Thursday, August 11, 2011

The Carbohydrate Hypothesis of Obesity: a Critical Examination

Introduction

I'd like to begin by emphasizing that carbohydrate restriction has helped many people lose body fat and improve their metabolic health. Although it doesn't work for everyone, there is no doubt that carbohydrate restriction causes fat loss in many, perhaps even most obese people. For a subset of people, the results can be very impressive. I consider that to be a fact at this point, but that's not what I'll be discussing here.

What I want to discuss is a hypothesis. It's the idea, championed by Gary Taubes, that carbohydrate (particularly refined carbohydrate) is the primary cause of common obesity due to its ability to elevate insulin, thereby causing increased fat storage in fat cells. To demonstrate that I'm representing this hypothesis accurately, here is a quote from his book Good Calories, Bad Calories:

This alternative hypothesis of obesity constitutes three distinct propositions. First, as I've said, is the basic proposition that obesity is caused by a regulatory defect in fat metabolism, and so a defect in the distribution of energy rather than an imbalance of energy intake and expenditure. The second is that insulin plays a primary role in this fattening process, and the compensatory behaviors of hunger and lethargy. The third is that carbohydrates, and particularly refined carbohydrates-- and perhaps the fructose content as well, and thus perhaps the amount of sugars consumed-- are the prime suspects in the chronic elevation of insulin; hence, they are the ultimate cause of common obesity.

There are three parts to this idea. I'll discuss them each separately.

Part I: A Defect of Fat Metabolism?

The first part of this hypothesis states that energy balance is not the ultimate cause of fat gain, it's the proximal cause. That is, Taubes is not disagreeing with the first law of thermodynamics: he understands that fat accumulation depends on how much energy is entering the body vs. leaving it. However, he feels that the entire industrialized world didn't just wake up one morning and decide to eat more calories, therefore something must be driving the increased calorie consumption.

He cited the research of Drs. Jules Hirsch and Rudy Leibel, various underfeeding and overfeeding studies, lipectomy studies, and evidence from genetically obese rodents, to demonstrate that body fatness is biologically regulated rather than being the passive result of voluntary food intake and exercise behaviors. He then advances the idea that it's an alteration in this body fat regulatory system that is behind obesity. This may sound familiar because I've written about it several times. So far, so good.

This is where he should have mentioned leptin signaling, and the circuits in the brain that regulate body fat mass, which would have taken the book in a more compelling direction. According to literally thousands of publications spanning nearly two centuries, the brain is the only organ that is known to regulate body fat mass in humans and other animals-- neither fat tissue itself, nor the insulin-secreting pancreas have the ability to regulate body fat mass as far as we currently know. Leptin is the system that Drs. Jules Hirsch and Rudy Leibel have shown in carefully controlled human studies is responsible for the metabolic defect Taubes alluded to (1). It's also the system that is mutated in the genetically obese rodents he discusses (2, 3). Yet it receives no mention in the book. This is a fork in the road, where Taubes discards a solid hypothesis in favor of a shaky one.

Part II: The Role of Insulin in Body Fatness

Insulin has many functions throughout the body. The primary role of insulin is to manage circulating concentrations of nutrients (principally glucose, amino acids, and fatty acids, the body's three main fuels), keeping them within an optimal range, and coordinating the shift between metabolic fuels that is required when a person consumes more of one or the other. Any time insulin suppresses fat burning, it increases carbohydrate and/or protein burning by an equivalent amount. That is what insulin does.

Insulin has a number of actions on fat and lean tissues that favor fat storage and suppress fat burning, and this is the crux of Taubes's basic argument in support of the idea that insulin causes fat accumulation. Some of these actions have been recognized for many decades. Taubes's idea is so simple, you might think someone had already thought of it. In fact, the idea has been around for a long time, but it has very little traction among obesity researchers today because it doesn't fit with a variety of basic observations, as I will explain.

The reason insulin suppresses fat burning is because it's a signal of glucose abundance. It's telling tissues to stop burning fat because carbohydrate is the available fuel. If you eat a meal of 500 calories of carbohydrate, you will burn that carbohydrate under the direction of insulin, which will also make sure body fat mostly stays inside your fat cells during the process. If you eat a meal of 500 calories of fat, you will burn fat instead of carbohydrate, but since you just ate fat, you aren't dipping into your body fat stores any more than you were when you ate carbohydrate. So even though insulin temporarily suppresses fat burning and the release of fat from fat cells when you eat carbohydrate, at the end of the day if you ate the same number of calories you end up with the same amount of fat in your fat cells either way. You now know more about insulin than many popular diet gurus.

As we are all on the same page (I hope) that the first law of thermodynamics applies to humans, for insulin to cause fat gain, it must either increase energy intake, decrease energy expenditure, or both. Let's see if that's true.

Let's look at the effect of insulin on food intake. To keep it as realistic as possible, let's compare satiety and subsequent food intake among foods that raise insulin to varying degrees. If calories and protein are kept the same, high-carbohydrate meals cause equal or greater satiety than high-fat meals, and equal or less subsequent food intake, despite a much larger insulin response (4, 5, 6, 7). Due to the insulin-stimulating effect of protein, low-carbohydrate high-protein meals can sometimes stimulate insulin to an equal or greater degree than high-carbohydrate meals, yet even in these cases higher insulin release is associated with increased satiety (8). Experiments in which investigators feed volunteers protein foods that stimulate insulin to different degrees show that the amount of satiety is positively correlated with the degree of insulin release (9), which is not consistent with the idea that insulin stimulates food intake. In the long term, low-carbohydrate diets suppress appetite in many overweight/obese people, however this is unlikely to be related to insulin.

If elevated insulin leads to increased fat storage and increased food intake, then experimentally elevating insulin in animals should replicate this (since insulin acts on fat cells in the same manner in humans and non-human mammals). However, this is not observed. Insulin injections at a dose that does not cause frank hypoglycemia do not increase food intake, and in some cases they even reduce it (48). Chronically increasing circulating insulin without causing hypoglycemia reduces food intake and body
weight in non-diabetic animals, without causing illness, contrary to what this idea would predict
(49, 50). If anything, insulin constrains food intake and body fatness, and research indicates that this action occurs via the brain. Insulin infused into the brains of baboons causes a suppression of appetite and fat loss, which is consistent with the fact that insulin and leptin have overlapping functions in the brain (10, 11). Knocking out insulin receptors in the brain leads to increased fat mass in rodents, suggesting that its normal function involves constraining fat mass (12). Insulin is also co-secreted with amylin, which suppresses food intake and body weight (13). This is why insulin is viewed by some obesity researchers as an anti-obesity hormone.

Now let's look at energy expenditure. If insulin is increasing fat accumulation due to a decrease in energy expenditure (presumably because elevated insulin is locking fat away inside fat cells), then people with higher fasting insulin should have lower resting energy expenditure. Lucky for us, that hypothesis has been tested. At least two studies have shown that higher fasting insulin is associated with a higher resting energy expenditure, independent of body fatness, not a lower expenditure (14, 15). If anything, this is the opposite of what the hypothesis would predict. How about post-meal insulin spikes due to eating carbohydrate? A number of studies have consistently shown that under isocaloric controlled conditions, substantially different carbohydrate:fat ratios do not influence energy expenditure in any measurable way, even over long periods of time (16, 17).

Therefore, if insulin doesn't increase energy intake (if anything, the combination of insulin and amylin that the pancreas releases in response to carbohydrate decreases it), and doesn't decrease energy expenditure, then how exactly is it supposed to cause energy accumulation in the body as fat? There is no energy fairy. Obese people are obese despite having higher fasting insulin, not because of it. The fact is, insulin spikes after meals temporarily decrease fat release from fat cells, but if you look at total 24 hour energy balance, insulin spikes, in conjunction with all the other hormones that are released in response to food ingestion, do not cause fat accumulation. This is exactly how you would expect the system to work if it were designed to constructively handle a wide variety of macronutrient ratios, which it is. Just as cholesterol did not evolve to give us heart attacks, insulin did not evolve to make us fat.

Now let's address the common sense arguments that are used to support the insulin hypothesis of obesity. These include:

These observations are all accurate, and at a glance, they seem to support the hypothesis. Manipulating insulin signaling can change fat mass, and obese people have higher insulin, so it must be involved in obesity, right? Unfortunately these arguments fall apart upon closer scrutiny, not because they're based on inaccurate observations, but because they're irrelevant to common obesity. In obesity as in most other conditions where insulin is high, elevated insulin is a symptom of insulin resistance, and the two occur in parallel. The pancreas secretes more insulin because the tissues can't "hear" it as well, so they need more of it to do the job. The more insulin resistance, the more insulin. The key point here is that elevated insulin in obesity is a compensatory response to insulin resistance, i.e. a reduced insulin signal. The cells are not seeing more insulin signaling, because they're insulin resistant, so it makes no sense to invoke increased insulin action to explain common obesity.

Arguments 1-5 listed above are cases where insulin levels and/or insulin sensitivity are changing independently of one another, either through a pathological process (islet autoimmunity), genetic manipulation (fat cell insulin receptor knockout), or through drugs. This is why they're irrelevant to common obesity, where insulin levels and insulin resistance rise in parallel, such that total insulin action is either maintained or diminished. If we want to do an experiment that's actually relevant to the question, we can use animal models that are genetically manipulated to maintain insulin sensitivity in response to fattening diets, which as expected eliminates the increase in insulin that is typically observed on these diets. These experiments show that fat mass accumulation does not consistently differ between animals that experience an increase in insulin, and those that don't-- they all get fat at approximately the same rate (17a, 17b, 17c).

In addition to what I just explained, both diazoxide and octreotide (argument #5) are extremely nonspecific drugs that have actions in the hypothalamus (brain) that would be expected to influence fat mass, so we actually have no idea if they act by reducing circulating insulin levels or through some other mechanism.

The idea of fat gain in insulin-treated diabetics (argument #3) is not as airtight as it might at first seem. On average, diabetics do gain fat when they initiate insulin therapy using short-acting insulins. This is partially because insulin keeps them from peeing out glucose (glycosuria) to the tune of a couple hundred calories a day. It's also because there isn't enough insulin around to restrain the release of fat from fat cells (lipolysis), which is one of insulin's jobs, as described above. When you correct this insulin deficiency (absolute or relative), obviously a diabetic person will typically gain weight. In addition, short-acting insulins are hard to control, and often create episodes where glucose drops too low (hypoglycemia), which is a potent trigger for food intake and fat gain.

So what happens when you administer insulin to less severe diabetics that don't have much glycosuria, and you use a type of insulin that is more stable in the bloodstream and so causes fewer hypoglycemic episodes? This was recently addressed by the massive ORIGIN trial (17d). Investigators randomized 12,537 diabetic or pre-diabetic people to
insulin therapy or treatment as usual, and followed them for 6 years.
The insulin group received insulin glargine, a form of long-acting
"basal" insulin that elevates baseline insulin throughout the day and
night. In this study, insulin treatment brought fasting glucose from
125 to 93 mg/dL on average, so it was clearly a high enough dosage to
have meaningful biological effects. After 6 years of
divergent insulin levels, the difference in body weight was only 4.6 lbs
(2.1 kg), which is at least partially explained by the fact that the
insulin group had more hypoglycemic episodes, and took less metformin (a diabetes drug that causes fat loss). A previous study found that three different kinds of long-acting insulin actually caused a slight weight loss over three months (17e). This is rather difficult to reconcile with the idea that elevated fasting insulin is as fattening as claimed.

In obesity, fat tissue is insulin resistant. The fat tissue of obese people doesn't suppress fatty acid release in response to experimentally elevated insulin or mixed meals as effectively as the fat tissue of a lean individual (18, 19). In fact, obese people release an equal or larger amount of fatty acids from their fat tissue than lean people under basal conditions as well (20, 21). If this is true, then why do they remain obese? It's simple: the long-term rate of fat entering the fat cells is equal to the rate exiting, or higher. There is no defect in the ability of fat cells to release fat in obesity, the problem is that the fat that is released is not being oxidized (burned) at a rate that exceeds what is coming in from the diet, therefore it all ends up back in the fat tissue.

While we're on the subject, let's address the idea of "internal starvation". Taubes suggests that people overeat because they can't access their fat stores due to elevated insulin. However, obese people have normal or elevated levels of circulating fat (22, 23), so how is that possible? The internal starvation model was interesting, if speculative, at the time it was proposed, however the evidence for it has simply failed to materialize. If anything, obesity is a condition of "internal excess".

Let's also address the claim that obese people don't necessarily eat more than lean people. Food records are notoriously inaccurate, however there is at least one way to measure total energy intake in a precise and unbiased manner. It is called the "doubly labeled water method" (DLW). DLW studies have shown that after controlling for confounding factors (gender, age, physical activity), obese people almost invariably expend more, and consume more calories than lean people (24, 25). Weight stable obese people have a higher energy flux out of fat cells, and a higher metabolic rate, but it is not enough to overcome the higher calorie intake that is also observed (26, 27). That has been repeatedly confirmed and it is simply a fact at this point.

If elevated insulin leads to fat gain, then this should be scientifically observable. All we have to do is look for people with different levels of circulating insulin (controlling for baseline fat mass), and see if it predicts fat gain over time. Fortunately for us, this has been studied many times. In most studies, insulin levels are unrelated to future fat gain, or people with higher fasting insulin at baseline actually gain less fat over time that people with lower fasting insulin (27a). In the most recent study, higher insulin (and insulin resistance) at baseline was associated with less fat gain over time, but this relationship was eliminated by adjusting for baseline fat mass, leaving no relationship between insulin and fat gain after adjustment (27b). Again, I don't see how this can be reconciled with the idea that elevated fasting insulin is the cause of common obesity.

Therefore, the insulin hypothesis is not consistent with basic thermodynamics, it's not consistent with research on the biological functions of insulin, and it's not consistent with observational studies. Obese people do not have a defect in the ability to release fat from fat cells and burn it, to the contrary. They release more fat from fat cells than lean people, and burn more of it. However, this is compensated for by a higher energy intake, and a higher rate of fat incorporation into fat cells that counterbalances the increased expenditure. This shows that insulin does not cause obesity by acting directly on fat cells to cause fat storage. To understand obesity, we have to understand what causes increased food intake, and that factor is not insulin.

Part IIB: Insights From Human Genetics

Genetic studies can give us important clues to the biological processes underlying common diseases. For example, common genetic variants associated with type 2 diabetes risk tend to be in genes that regulate the insulin-secreting pancreas (38). This tells us, as one would expect, that pancreatic function is important in diabetes. What does genetics tell us about the mechanisms of obesity?

There are a handful of rare single-gene mutations in humans that lead to severe obesity. Every single one that has been discovered to date that does not also result in deformity (nondysmorphic monogenic obesity) is in the leptin signaling pathway (39), and even those that do result in deformity all influence how the brain regulates body fatness, suggesting that body fatness is normally regulated by the brain, not by fat tissue. From a 2009 review paper (40):

There are now at least 20 single gene disorders that clearly result in an autosomal form of human obesity. Notably, so far all these disorders affect the central [i.e., brain] sensing and control of energy balance.

Genome-wide association studies (GWAS) give us a different perspective-- they look for common genetic variants that associate with higher or lower body mass index (BMI) in the general population. These are not mutations that make genes non-functional, they are simply common differences between genes that in some cases subtly influence their activity. Of the numerous common gene variants that have been found to associate with BMI variability, and whose function is known, the large majority are expressed in the brain, particularly the hypothalamus, and some are in the leptin signaling pathway (41, 42). That's why these papers often make statements like this (43):

...when we look at the information gleaned from the past 15 years of molecular genetic activity we cannot avoid concluding that, as much as type 2 diabetes is clearly a disease in which pancreatic beta-cell dysfunction is a critical element, obesity is a condition in which inherent genetic predisposition is dominated by the brain.

Many of our associated loci highlight genes that are highly expressed in the brain (and several particularly so in the hypothalamus), consistent with an important role for CNS [central nervous system] processes in weight regulation.

If insulin action on fat cells is a dominant factor in obesity, why don't genes linked to insulin signaling show up at the top of the list in these studies? There are enough proteins that regulate insulin secretion in the pancreas and insulin signaling in fat cells that one would expect genetic variability in these genes to turn up frequently if they were important regulators of fat mass, but instead the list is dominated by genes that relate to the brain, and leptin signaling in particular. This is consistent with a huge body of literature implicating the brain in body fat mass regulation and the development of obesity.

I've already demonstrated that it makes no sense to invoke insulin as a mechanism between carbohydrate consumption and body fatness. Another problem with the hypothesis is a thing called the insulinogenic index (II). The II is simply a measure of how much eating a food increases insulin, per unit calorie (28). It turns out, it doesn't correspond with the carbohydrate content of a food very well. In particular, protein-rich foods such as beef can increase insulin secretion as much as certain starch foods such as pasta, or more. High-protein diets, as many of you know, aid with weight loss. Some have suggested that this is because of glucagon release by the pancreas in response to protein. That may well play a role, but if we are going to invoke glucagon, then aren't we acknowledging that other signals besides insulin play an important role in this process? That's the larger point I'm trying to make here-- you can't just look at insulin, you have to consider amylin, glucagon, GLP-1, ghrelin, leptin, stomach distension, and all of the other short- and long-term signals that are activated in response to nutrient ingestion and changes in body fat mass. These collectively regulate food intake and long-term body fatness via the brain.

The other problem is that refined and unrefined carbohydrates often have a similar II. Pasta made from white and whole-grain wheat have the same II, and the same goes for white and whole-grain bread (29). Doughnuts and cookies are on par with whole grain bread. So post-meal insulin is not a compelling explanation for the potentially different effects of protein, unrefined carbohydrate, refined carbohydrate and sugar on body fatness.

I think it's likely that refined carbohydrate and sugar can contribute to obesity, but by what mechanism? Insulin is not a compelling explanation.

But let's forget about insulin for a minute. Without worrying about the mechanism, let's simply consider the hypothesis that carbohydrate consumption per se causes body fat accumulation. At this point, I know some people will be insisting that Taubes is talking specifically about refined carbohydrate, not carbohydrate in general. Taubes does repeatedly suggest in GCBC that all carbohydrate is fattening, although refined carbohydrate is more fattening. Otherwise, why would he write "...carbohydrates, and particularly refined
carbohydrates... are the ultimate cause of
common obesity", rather than simply stating "...refined
carbohydrates... are the ultimate cause of
common obesity"? This wording, used throughout CGBC, implies that all carbohydrate is fattening to some degree. There is also the example in GCBC of the Massas tribe fattening on unrefined sorghum, described below. If Taubes doesn't think unrefined carbohydrate is fattening, then why does he recommend a low-carbohydrate diet rather that suggesting that people replace refined carbohydrate with unrefined carbohydrate?

To address this hypothesis, first let's find some cultures that have a very high carbohydrate intake and see how fat they are. Let's start with a culture that eats more carbohydrate than any other I know: the New Guinea highland tribe at Tukisenta that was studied extensively in the 1960s and 70s. They ate 94 percent of their calories as carbohydrate, mostly from sweet potatoes, for a total calorie intake of 2,300 kcal/day in men and 1,770 kcal/day in women. Investigators found them to be fit, lean and muscular, with no sign of protein deficiency (Trowell and Burkitt. Western Diseases. 1981).

West Nile district, Uganda, 1940s. The diet consisted of millet, cassava, corn, lentils, peanuts, bananas and vegetables (Trowell and Burkitt. Western Diseases. 1981). Despite food abundance, "in the 1940s it was quite unusual to see a stout man or woman." "In recent years, however, a fair number of upper-class middle-aged West Nile women have begun to look rather stout, and some men have become very obese, especially those who hold lucrative posts and can purchase whatever food they like." This corresponded with an increase in "sugar, cooking oils, milk, fish and meat" and a corresponding decrease in "home-grown starchy staple foods." This same scenario has happened to hundreds, if not thousands of African communities whose traditional diets are very high in carbohydrate.

Northern Cameroon, 1980s. The Massas tribe (also spelled Massa) is known for its overfeeding ritual called Guru Walla, which Taubes describes in GCBC:

The Massa tribe of northern Cameroon fattens their males using both milk and a porridge made from sorghum, a corn-like grain that provides sweet syrup from the stalk. One man gained seventy-five pounds on a ceremonial binge. The average weight gain tends to be fifteen to twenty pounds using milk and porridge. The Massa are cattle herders and their staple diet is primarily milk. This fattening comes about by the addition of carbohydrates (sorghum) almost exclusively.

Taubes states here that the typical diet is "primarily milk", therefore by inference, low in carbohydrate. Let's follow his reference and see what it says. It leads to a freely accessible paper by Drs. Igor de Garine and Georgius J.A. Koppert titled "Guru Fattening Sessions Among the Massa" (30). The Massas indeed herd cattle, but "their main use is not as food." The typical diet (not during overfeeding) is described as containing 516 grams of carbohydrate per day, and only 32 grams of fat (Table VIII). The typical diet is 81% carbohydrate, and primarily based on sorghum, according to his reference. This account is consistent with other freely accessible references in respected peer-reviewed journals (31). These people are lean on their typical high-carbohydrate fare until they deliberately overconsume a mixture of sorghum and milk.

Most of Asia, 20th century. Many Asian countries, including China, Japan, Taiwan and India, have a traditional diet that is very high in carbohydrate. In many cases, the dominant carbohydrate was white rice, a refined carbohydrate. Yet traditional Japanese, Chinese and Southern Indians eating mostly white rice were renowned for their leanness. Any plausible hypothesis of obesity needs to account for these observations.

Kitava, 1990s. Dr. Staffan Lindeberg showed that the Kitavan diet is 69% carbohydrate, mostly from taro, breadfruit, sweet potatoes and cassava (32). Thus, their diet would have had a high glycemic load and high II. They also obtain 50 g/day of carbohydrate from fruit, most of which would presumably been sugar (unrefined). Yet there was no obesity on the island, and only a few individuals that were slightly overweight (33). Fasting serum insulin was low, consistent with other high-carbohydrate cultures. Dietary carbohydrate does not cause insulin resistance.

Pima, 20th century. The Pima of New Mexico currently have one of the highest obesity rates in the world, on par with Nauru. It is rather ironic that Taubes uses them as an example in GCBC, when they are at odds with his hypothesis. The Pima were first contacted in 1539 by the Spanish, who apparently found them to be lean and healthy. At the time, they were eating a high-carbohydrate, low-fat diet based on corn, beans, starchy squash, and a modest amount of gathered animal and plant foods from the forest and rivers in the area. In 1869, the Gila river went dry for the first time, and 1886 was the last year water flowed onto their land, due to upstream river diversion by settlers. They suffered famine, and were rescued by government rations consisting of white flour, sugar, lard, canned meats, salt and other canned and processed goods. They subsequently became obese and have remained that way ever since. Their diet consisted mostly of bread cooked in lard, sweetened beverages and canned goods, and they also received salt. More recently, their diet has modernized but still relies heavily on processed food (34, 35).

Finally, let's take a look at my country, the United States of America. Total calorie intake has increased since the 1970s, and the excess calories came mostly from carbohydrate (primarily refined), and also from fat and protein to a lesser extent. But what happens if we go back further, to the turn of the 20th century? Here's our per capita macronutrient consumption in calories per day from 1909 to 2006, according to USDA data*:

If we take the long view, the only thing that has consistently increased is fat, not carbohydrate. The prevalence of obesity was very low at the turn of the century (36), yet our diet was 57% carbohydrate by calories, much of which came from white flour. These USDA figures account for food produced and consumed on farms and in home gardens, in addition to what passed through commercial sales (37). Why would carbohydrate promote obesity today when it didn't 100 years
ago, and it continues not to in numerous high-carbohydrate cultures
around the world?

Conclusion

I hope you can see by now that the carbohydrate hypothesis of obesity is not only incorrect on a number of levels, but it may even be backward. The reason why obesity and metabolism researchers don't typically subscribe to this idea is that it is contradicted by a large body of evidence from multiple fields. I understand that people like ideas that "challenge conventional wisdom", but the fact is that obesity is a complex state and it will not be shoehorned into simplistic hypotheses.

Carbohydrate consumption per se is not behind the obesity epidemic. However, once overweight or obesity is established, carbohydrate restriction can aid fat loss in some people. The mechanism by which this occurs is not totally clear, but there is no evidence that insulin plays a causal role in this process. Carbohydrate restriction spontaneously reduces calorie intake (as does fat restriction to a lesser extent), suggesting the possibility that it alters body fat homeostasis, but there is no compelling evidence that this happens due to a hormonal influence on fat tissue itself. The brain is the primary homeostatic regulator of fat mass, just as it homeostatically regulates blood pressure, breathing rate, and body temperature. This has been suspected since the early brain lesion studies of the 1940s (47) and even before, and the discovery of leptin in 1994 cemented leptin's role as the main player in body fat homeostasis. In some cases, the setpoint around which the body defends these variables can be changed (e.g., hypertension, fever, and obesity). Research is ongoing to understand how this process works.

* I've adjusted these data for loss, using the standard USDA adjustment of 28.8 percent, to get a more accurate picture of actual consumption rather than sales. I've also adjusted for an artifact in the fat data in 2000, where there was a big spike due to a change in the assessment method.

Terrific explanation of otherwise difficult-to-follow interactions, but I'm confused on one point. How can we draw useful conclusions about the effects of serum glucose or insulin from 'traditional' tribes and cultures, which have constant activity all day long? Similarly, Americans were a majority of manual laborers earlier in the last century. Is the effect of a high carbohydrate diet or of chronically elevated insulin the same in active and sedentary individuals? Do our hormones work the same way irrespective of muscle mass and activity level? For that matter, do we know if muscular, lean, active people ever become 'insulin resistant' ?

I like the breakdown of the CHO hypothesis. One thing that I noticed is you are speaking in the context of a "normal" obese person.What is your stance when the person is a T1 diabetic? I was considered obese until my pancreas began shutting down. I easily lost 60+ pounds in 6 months. No matter what I ate, I was losing weight like crazy, drinking water like crazy, and producing a modest amount of ketones. Once I was diagnosed, I was put on a basal insulin regime, and so I put the weight back on.Today I am back up to almost my pre-pancreatic meltdown weight.

It is well known in the Diabetic Online Community that the easiest (albeit dangerous way) to lose weight is to stop taking your insulin. It is called diabulimia.

I agree that it's too simplistic to throw carbs under the bus. Protein will also provoke an insulin response = as every T1 diabetic knows.

I know that carbs without the insulin is bad for me. Without the insulin, I would die.

How do we refute that body of evidence? Insulin drives energy storage - which leads out to fat. I am living proof.

I don't know if this a request or a statement, but I second it if it is a request, and I look forward to future blog posts if it is a statement!

And I believe I'm in the majority when I say I don't want to read a bitter takedown of Taubes. Calm, well-reasoned, and well-referenced blog posts will continue to do nicely. Drama is seriously overrated.

Stephen, Thank you for the quick lunch we had at AHS, it was a pleasure getting to know you, even a little. And thanks for this article. As someone who believed in the low carb model you've thrown my world sideways. In a good way. Always keep learning, eschew dogma.

So why is this the first genuine public criticism of Taubes? Why hasn't this hypothesis and analysis been disseminated before? Frankly, the scientific community is doing a dismal job of educating even the most interested in the subject. I am grateful for this article but still don't know how to eat!

Stephan,I have always enjoyed your blog posts and many of them were impressive and well referenced but you have simply outdone yourself with this one! Great post and nice job on staying classy, no need to become bitter for being an honest diligent open minded researcher.

You referenced that higher fasting insulin levels are connected to a higher resting energy expenditure, which protects against weight gain. Could you explain why the Kitavans had such low fasting insulin levels?

@ KURT "My wife suggests paying attention to whatever food you look forward to eating when you first wake up, and eliminate that"

lol, im sorry but that's HORRIBLE what a miserable life you must live. ME? i do the exact opposite. love to eat chocolate and chocolate milk. so i just eat chocolate and drink whole milk every single day. lotsa sucrose.

You're not paying attention to what I said, so maybe you're a bit confused.

These are food reward related weight loss tips.They are highly effective if you need to lose weight.

I personally weigh 155 and have a 30 inch waist. My wife is 5' 6" and weighs 117. We are both over 50.

So we don't do these maneuvers because we don't need to. I don't eat the ice cream because I now have zero desire for it, just like stephan no longer craves donuts. My wife and I do not have a life that revolves around food, but we truly enjoy what we eat when we eat it.

So I assure you that you in fact know nothing at all about my life or whether it is horrible or not.

But I am very happy that every day is pure and utter bliss for you, whatever addictive substance you may be using to achieve such an unnatural state.

Stephan, I was so excited to see you tackle the carb issue, and this post was if possible even more helpful than I expected. It prompted me to finally come out of the closet as a long-time reader and fan of your blog.

I'm also a big fan of Gary Taubes, and deeply appreciate the time and effort he put into researching and systematically demolishing the lipid heart hypothesis. He's only human, though, so it comes as no surprise that he is only half right. I hope he realizes that even if the carbohydrate hypothesis is wrong, the rest of his work is still valuable.

Anyway, thanks again for the fantastic work, Stephan. Your posts are so well-reasoned and well-referenced that it's almost impossible to not take your ideas seriously.

I had assumed all of the people Taubes listed in his Acknowledgments in Why We Get Fat agreed with his conclusions, and I did notice Stephan Guyenet and Mike Eades among the draft readers. I will not make that assumption again. I'm glad GT was rude, if that's what it took to inspire this critical analysis. I prefer when people treat each other with kindness, but my reason to come here is for facts and reasonable hypotheses about what is likely to keep my body and mind healthy. If rudeness is what it takes to keep the discussion flowing, go to it.

I'm sure in time that I'll get over finding out there is no energy fairy.

Do you suppose reducing either the carbohydrate or fat macronutrient (but not both) might have a big effect on the palatability of food? I don't like a dry potato, and I don't like butter solo, but together with a dash of salt and rosemary....

Thanks to the source-twisting journalist with wild imagination the idea of carbohydrates making one fat is deeply sealed into the Western psyche. In the USA you guys are civilized and actually have a debate. In Scandinavia the confused LCHF MD's have propagated their message to the extent that people are afraid to even eat rice.

Thank you for a thought-provoking and well-done post. It got me thinking...and reading. I would love to see a discussion on how the brain, and peripheral tissues, regulate energy. In my view, insulin and the carbohydrate/protein that releases it is crucial in obesity treatment (not necessarily in the development of obesity, for reasons beyond my knowledge).

I think AMP-activated protein kinase (AMPK) is important in the discussion. AMPK is key in energy homeostasis and hypothesized to be one player in mediating the effects of leptin, insulin, glucocorticoids, cannabanoids, adiponectin, and ghrelin on anabolic vs. catabolic processes (Lim 2010).

I believe that insulin has a large role in creating the "defect in fat metabolism" you refer to in your first point regarding Hirsch and Leibel's work. Insulin's effect goes past caloric intake and expenditure alterations and involves the hormonal effects from signal transduction off the insulin receptor, similar to the effects of leptin.

The effect of insulin and leptin on cellular energy storage/usage is mediated through the AMPK pathway. I think a compare/contrast of the two hormones is important because if you recognize that leptin is hormonally altering the state of cellular fuel stores, you have to accept that insulin does the same.

In the hypothalamus, leptin decreases appetite and energy intake through AMPK inhibition (Minokoshi 2002, 2004, Mountjoy 2007). Insulin, in the hypothalamus, does the same via the same AMPK mediators (Minokoshi 2004). So far I'm with you, both insulin and leptin decrease appetite, much like you stated.

However, in the periphery at the liver, skeletal muscle, and adipose tissue the two hormones hold opposing roles.

Leptin activates AMPK at the liver, skeletal muscle, adipose, and heart (Steinberg 2003, Lim 2010 and Brabant 2005). Adiponectin does the same. This leads to less hepatic glucose production, less fat storage, more fat usage, more glucose uptake, etc.

Here's the kicker, insulin downregulates and inhibits AMPK at the liver, skeletal muscles, and adipose by activating protein kinase B/Akt complex (Kovacic 2003 and Horman 2006). This drives glycogen production (another inhibitor of AMPK), fat synthesis, and hepatic glucose production. This is the exact same effect that glucocorticoids (the lipodystrophy seen in chronic corticosteroid exposure or cushing's disease) and ghrelin have at the level of the adipose tissue. Do you say that chronically elevated cortisol isn't responsible for the defect in fat metabolism seen in lipodystrophy? I say hyperinsulinemia seen in metabolic syndrome and obesity is similarly responsible for a large number of patients.

I can say that in diabetics insulin therapy causes virtually all to gain weight, while metformin (a peripheral AMPK activator) cause a mild weight reduction in most cases. In my opinion, the optimal treatment of obesity includes a high fat diet that limits carb/protein intake to prevent subsequent insulin release is optimal.

If you believe leptin to exert an effect on fat metabolism so must insulin, through the same AMPK pathway.

Interesting about the effects of infused insulin on the baboons. Under what circumstances would we have an insulin response directly to the brain without food ingestion? It's clear that the roles of hormones are many and complex. Do you think uncoupling the response from its stimulus tells the entire story?

Your falsification of hypothesis #2 is simply restating the conservation of energy. The boundary conditions that are the Laws of Science can never be violated. They are always true all the time, hence laws.

Last question, is it possible for someone to have low or normal fasting blood glucose and elevated fasting insulin? If such a condition is possible, what do you suppose the physiological effects would be?

Great post - even more than usual! I am curious, though, what you think of this Princeton diet study, in which the "Atkins" diet (in practice just moderately low-carb) beat out three others. But the interesting thing to me is that among dieters who had no insulin resistance, the Atkins diet performed roughly as effectively as the low-fat plan, whereas the dieters who were insulin resistant experienced roughly twice the success versus those on the low-fat diet.

ItsTheWooo2, I think the problem is that many researchers and scientists think in a vacuum. For instance, they'll look at a study where participants are given different diets with various amounts of CHO, look at the immediate glucose and insulin response, then give a questionnaire about satiety 15 minutes after eating that proves that insulin is satiating because people on the high CHO diet with high levels of insulin are more sated 15 minutes after eating a CHO heavy meal, before the hypoglycemia has kicked in.

ITW: "[Leptin elevation in obesity] does NOT mean you are resistant to leptin. It does not mean you are fat because of leptin. Leptin elevation in obesity is an obvious and expected finding, it describes nothing."

SG (from an earlier post): "Leptin is a hormone produced by body fat that reduces food intake and increases energy expenditure by acting in the brain. The more fat a person carries, the more leptin they produce, and hypothetically this should keep body fat in a narrow window by this form of "negative feedback". Clearly, that's not the whole story, otherwise obesity wouldn't exist."

Regarding insulin and fat storage:

ITW: "What occurs in (garden variety) obesity . . . is that an excessive amount of insulin is produced in an attempt to reduce the blood glucose level. This suppresses fat release abnormally and increases fat synthesis equally abnormally . . . The end result is the person stores their nutrients as fat, with an attending abnormal increase in appetite (which is expected when blood FFA drop and blood glucose drops)."

SG: "[I]nsulin signaling in fat tissue depends both on the concentration of insulin around, and on the sensitivity of cells to that insulin. In obesity, fat tissue is insulin resistant. How do I know? Because the fat tissue of obese people doesn't suppress fatty acid release in response to experimentally elevated insulin or mixed meals as effectively as the fat tissue of a lean individual (18, 19). In fact, obese people release an equal or larger amount of fatty acids from their fat tissue than lean people under basal conditions as well (20, 21)."

ITW: "In the real world, there is no euglycemic clamp. There are dips and surges. The surges do not come with a glucose IV, which prevents FFA from dropping due to chronic glucose oxidation. The fact that the fatties had higher FFA than the skinnies only shows what we all know - fat people have fatter cells, fat people are not as sensitive to insulin, etc. DUH ten times over. "

M.B. As far as I can tell, of the studies Stephan cited, only one involved a euglycemic clamp.

Regarding insulin and appetite:

ITW: "It's well documented that slight increases in insulin cause an interest in food and eating in even normal subjects."

SG: "If calories and protein are kept the same, high-carbohydrate meals cause equal or greater satiety than high-fat meals, and equal or less subsequent food intake, despite a much larger insulin response (4, 5, 6, 7). Due to the insulin-stimulating effect of protein, low-carbohydrate high-protein meals can sometimes stimulate insulin to an equal or greater degree than high-carbohydrate meals, yet even in these cases higher insulin release is associated with increased satiety (8).

ITW: "Regarding your "evidence" that a carbohydrate rich meal suppresses appetite more than a fat rich meal... the abstracts do not define carbohydrate rich and fat rich."

M.B.: The free full texts do, however.

ITW: "It is well understood that adding fat to a high carbohydrate meal will typically increase insulin levels and thus fat storage/hunger."

M.B. As Stephan specified, the high-carb meals produced a greater insulin response than the high fat meals and equal or less subsequent food intake.

Regarding insulin and energy expenditure:

ITW: "It is entirely possible - and actually par for the course in obesity - for an increasing body fat level to go along with very high metabolic rate."

S.G.: "At least two studies have shown that higher fasting insulin is associated with a higher resting energy expenditure, independent of body fatness, not a lower expenditure (14, 15)."

M.B. So everybody agrees that insulin does not decrease energy expenditure.

There's one part of what itw2 is saying that jibes with my own experience... if I my blood sugar gets to say, 140 or higher, I tend get ravenously hungry a few hours later. And the only way to get my blood sugar high is by eating a large portion of carbs.

However this effect does not occur when I eat food that spike insulin without spiking glucose.

Also like several other people here, incorporating more starch in my diet (as long as it is in moderate amounts, and not consumed with any oxidized fats) has actually improved my blood sugar control.

So it does seem plausible to me that eating carbs (and especially carbs and fats together) could lead to overconsumption in at least some people (this is why low carb diets tend to work for the obese). However it probably requires some degree of metabolic damage. And the causal factor looks to be glucose, not insulin.

This is all very interesting! Especially the fact that most of us (well I did)believed in the low-carb hypothesis, although it was obvious that many people of this earth have eaten/eat a lot of carbs. The hypothesis turned into a (relgious) belief with people defending it like hell and/or attacking people who believe something else. Another thing that I miss in this whole debate is: metabolism: how is food digested and metabolized? For instance one can train the Type 2A muscles to prefer to burn fat in stead of sugar/glucose; in that case one may eat a lot of sugar and carbs/ without getting fat. Who knows, probably all those indigenous people have that kind of muscles, so they metabolize fat and glucose very differently than most of sedentary carb/sugar/fat eating Western people...

By the way a very interesting study about what J just said about the change of function of the muscles and its impact on hormones, you may find here:https://docs.google.com/viewer?a=v&pid=explorer&chrome=true&srcid=0By7LGCdd0SR9NDdmYTAyMTAtNmUxNS00NTdhLWI5NTgtN2FhMmE2ZmZmODQx&hl=nl

S.G.: "This is consistent with the idea that elevated fasting insulin protects against body fat accumulation, not that it contributes to it."

ITW: "How can anyone call themselves a PhD in the neurobiology with an interest in obesity and write that!"

M.B. If he had just presented a solid argument and references to support it.

Here I have a minor quibble. High fasting insulin is the result of obesity and adipose IR not the cause of it. Elevated fasting insulin is not protective against body fat accumulation, it is the body's attempt to protect it from its already accumulated fat! This is what a huge body of post WWII research clearly demonstrates. It's somewhat of a fat cell/pancreatic feedback loop: Overstuffed adipocyte becomes IR -> releases too much NEFA -> stimulates basal insulin production so as to compensate for adipocyte IR and prevent excessive NEFA release.

Gary's writing is so damned persuasive and catching, that it's hard not to be convinced (and angry) after reading GCBC. I remember how I secretly wished the Kitavans to please go away after I finished the tome ;-). I suspect many people had similar bouts of cognitive dissonance, but most of them soon came to their senses again, after remembering for example Staffan Lindeberg's observations. I would like to mention one thing. Stephan says that most scientists don't take Gary's carbohydrate hypothesis seriously because of what Stephan (and CarbSane) eloquently argue. That might be true for his direct peers, but I seriously doubt if the arguments of his falsification are common knowledge among the majority of specialists in human nutrition. This level of understanding is certainly not the norm among Dutch scientists (let alone dieticians), all arch enemies of Taubes. I have asked several Dutch specialists in human nutrition to debunk GCBC, but I never got a decent explanation. Had they known what Stephan presents here, they would have shouted it from the rooftops. Dogma is rife in academia and the fact that the carbohydrate hypothesis doesn't hold water, does not change that.

I think Taubes' biggest contibution is endlessly repeating the phrase "fattening carbohydrates" referring to the kind of foods that are produced in factories that neither you or he or people in pre-industrial cultures eat. Think how powerful the phrases "artery clogging saturated fat" or "healthy whole grains" have been in shaping the American diet. Only a tiny percentage of people who read Taubes follow the science, most of us are just trying to figure out what to eat.

"...Part of this response is hunger and increased food intake. However, this system is not activated except in severe hypoglycemia, which is rare except in diabetics, thus it is not relevant to common obesity."

I get that effect after eating excessive carbs. A few hours later I'm ravenous, and often shaking from hypoglycemia. If I eat low-carb, this never happens. It's one of the primary reasons I'm eating low-carb, because I hate that feeling... I'm not full-on diabetic, however.

I really like the Gary Taubes that I've seen in interviews and presentations. There, he's so laid back and eloquent. But he's also from New York. He's also from the physical sciences. You should see their debates! Health Science needs a little spice in their fora.

He has said repeatedly that he gets really frustrated and angry at mainstream theories of obesity. Maybe he was just afraid that this alternate explanation was going to derail all the good accomplished?

I still like Mr. Taubes. I still think he's mostly well composed, intelligent and well spoken.

In a similar vein, I have a question about the macronutrient studies stephan cited. Is it possible that prior meals are a factor in that one time satiety measure? For instance, when I eat high fat, I find high fat meals more satiating. When I eat high carb, the high carb meals become satiating. I also roam the house looking for fat like a zombie after brains... but that's beside the point.

I'm not a doctor or a researcher but from first hand observation I can say that when I eat grains and starches like potatoes, I gain weight. When I reduce them to under 80 grams/day or so I lose weight. All the while keeping my calorie count equal.

I believe the insulin-drives-fat hypothesis has a lot going for it. I'm going to stick with what works for me.

A great post - I continually feel that it's less simple than I previously thought.

And yet I do feel ItsTheWoo2 makes some good points and shouldn't be so easily dismissed.

It seems Stephan has obviously demonstrated you can eat plenty of carbs and be very healthy (Kitava, Okinawa, etc). I feel that he has demonstrated hyperpalatibility and leptin disregulation are important factors in obesity. Perhaps even the dominant factors?

But I still don't feel that he has disproven the idea that, once an individual is "metabololically broken," post prandial insulin spikes are cripplingly obesogenic. Remember, post prandial basically describes most of a person's day if they eat 4-6 small meals, especially considering that it takes a longer time for blood sugar to lower (2-3 hours), and thus they would have elevated insulin for as much as 16-18 hours of their day. So yes, one shot of insulin might not be the problem, but if your insulin levels are severely elevated for 3/4 of the day, couldn't that be severely problematic?

I feel like the mechanism by which leptin and insulin interrelate needs to be explained a bit more. That low-carb diets are simply lower reward diets is plausible, and I might be able to get behind it. But still, it seems like controlling getting someone with hyperinsulinemia back to cumulatively low levels of insulin has to be a good thing, right?

If I am obese and have chronically high levels of insulin, then getting those levels back down has to be beneficial, no?

OK ... I've seen this New Yorker thing enough times that this NY'er has to weigh in. Indeed I think the buildup of the exchange around the internet had me thinking GT was a far bigger jerk than he came off. Still, the last dig was unmistakable hubris and arrogance and a whole host of adjectives, none of them favorable. I've taken friends from all over the country to NYC, who've never been, and they are dumbfounded by how nice most folks are to them. Point being, this whole notion of a NY attitude is way overblown and a sorry excuse for Taubes' behavior.

I might also suggest that Gary has a blog on which to make things right, and I would suggest he doesn't wait three months ...

Good writeup that overall jives well with my "evolving perspective" on the issue.

My impression is that Taubes has been (somewhat inconsistently) backtracking on the carbohydrate hypothesis (as expressed in GCBC), mostly because of the implicit critique from Lustig.

Overall, it would be strange if one of the three major macronutrients available for human nutrition would induce metabolic derangement in itself. The notion is strangely similar to that animal fats cause heart disease...

Some related thoughts, all mixed up:

- IIRC, USDA data from before WWII should be taken with a scoop of salt or so, but that´s a minor issue. (We can observe a lack of metabolic derangement in present-day high-carbohydrate populations).

- I don´t find it strange that low-carb approaches are effective in treating obesity. If the core problem is one of leptin resistance (as seems likely to me), brought on (probably in most cases) by hyperinsulenemia, reducing insulin release seems like a workable approach for those unable to get a prescription for octreotide.

- If we take Lustig at his word, Insulin brings on satiety because it is closely coupled with leptin, IIRC. It is only when leptin resistance is induced by chronic hyperinsulenemia that insulin release becomes both larger and problematic.

- Quick comment: “If anything, obesity is a condition of "internal excess". I don´t think it´s reasonable to claim that obese people are *actually* starving. However, it seems like a pretty good term for describing leptin resistance. Your body might not be starving, but it thinks that it is.

- So, what agents cause the problem? My personal candidate list:

- Fructose in larger amounts.

- PUFA:s.

- Industrial Trans fats. (PUFA:a and trans fats are what constitute that fat increase during the obesity epidemic that you note above)

All pretty new at present concentrations in the diet, and all have increased in consumption along with the obesity and diabetes epidemics. There are also credible mechanisms in place to explain why they could cause hyperinsulinemia.

"In Scandinavia the confused LCHF MD's have propagated their message to the extent that people are afraid to even eat rice."

If they are overweight (and if they are reading diet blogs, odds are that they are), that´s probably not a bad thing. We aren´t discussing effective therapies against excess weight here, just causative factors.

As an aside: What makes me the most cautious about disregarding carbohydrate intake completely for weight regulation is personal experience, but there are some obvious entanglement problems.

In all honestly, I am rapidly coming to the conclusion that there is far too much "intellectual masturbation" taking place in regards to wondering what makes folks so darn fat these days.

I think "food reward" hypothesis is very solid...BUT I think a much simpler way of looking at it is that people tend to overeat really good tasting food.

I also think "carb-lipid combos" cause overeating. Not in a hormonal sense at all...but rather because when you are always eating foods that are high in BOTH carbs and fats it's all too easy to ingest excess calories!

For instance how much oil would you eat if I gave you a cup of oil? Gross right? But if I fry some sugar and flour in that oil, you'll eat them donuts baby!

How much PLAIN white rice will a person eat? Probably not that much in terms of calories. But how many calories will you take in if you fry that rice in butter?

"In all honestly, I am rapidly coming to the conclusion that there is far too much "intellectual masturbation" taking place in regards to wondering what makes folks so darn fat these days."

I dunno, given that the problem is

1.) Huge, in terms of both cost and unhappiness.

and

2.) Unsolved and rapidly growing.

I´m happy to see more "intellectual masturbation". The more relaxed and back-and-forth the better. There´s no shame in being wrong, as long as you are willing to keep a somewhat open and relaxed mind along the way. (Would you trust someone who has never been wrong?).

This comment refers to the glee with which people are happy with the article, and not about the article itself.

Dang it! All this arguing and sniping doesn't help us who still struggle with body comp issues.

First our savior was going to be low-carb, then it became low-carb paleo, now, what, high carb paleo? A blogger who may say "farewell to paleo" just leaves the rest of us sitting in the dirt of desperation. What works for active, lean athletes may not work for us who have enjoyed neither fitness nor energy.

The whole debate just makes me distraught, because like several other posters have mentioned, we still need to decide what to eat!

And all this recent debate over carb levels has not mentioned other possibly important longevity factors, like AGE production, IGF-1 signaling, or mTOR signaling.

Since my primary goal is body comp and my secondary one is longevity, it tends to make me cling closely to the ideas of authors like Nora Gedgaudas (for longevity) and Robb Wolf (for body comp).

The research I'd like to see, besides carb levels is, for longevity, 1) how often should we be in ketosis; 2) what protein level is appropriate; 3) is "pulsed" protein intake better than consistently low (or high?) protein intake?

Please stop gleefully sniping at each other, and let's find the research answers to these and other questions.

"This comment refers to the glee with which people are happy with the article, and not about the article itself."

I dunno about the glee. I like much of what Taubes writes, but I think that he is wrong on carbohydrates per se causing obesity. Hell, I even think Taubes thinks that Taubes is wrong on this, but it seems he hasn´t quite arrived at a coherent stance on this point.

I know that others here, like Kurt, have no glee on the issue. I reckon that we just like good writing on issues that we are interested in. I will read any response from Taubes with great interest.

"Dang it! All this arguing and sniping doesn't help us who still struggle with body comp issues."

Not now, but hopefully in the future.

"First our savior was going to be low-carb, then it became low-carb paleo, now, what, high carb paleo? A blogger who may say "farewell to paleo" just leaves the rest of us sitting in the dirt of desperation."

I doubt anyone has cast paleo to the wolves - I can´t think about a better framework for thinking about lifestyle and diet.

I'm just a regular girl. No science background, but I work in the area of health and I observe obsessively the way my own system operates and I observe people and how they operate, move, eat, think, etc. on a daily basis.

I think while we are all built generally the same, there are chemical differences. Some we are born with and they show themselves (or don't); some arise from our environment. And, we change over time. Just like you don't go through puberty forever with its hormonal eruptions.

I remember the exact moment something in my brain switched in adolescence and I craved sugar. And anything that contained/"turned into it"...bread, pasta, etc. Not fruit, though. Different 'feeling' response in my body & brain. It was carbs & sugars from these other sources. I should share, too, that this attachment formation to sugars began at a very stressful time in my life.

I discovered later that sugar addiction and alcoholism run in my family. I didn't start developing a potentially hazardous taste for wine (not beer), rum & vodka until my late 20's. Before that, carbs & sugars would do.

And when my blood sugar spiked which it always did, I had to have 2 large glasses of orange juice & a glass of milk & then some cheese to make it go away.

I have never been fat - I carry, generally, 10 pounds extra - no more. I exercise a lot and in the past years have been reining in my sugar intake. I am hyper aware of my sensitivity to sugar and have battled it hard my whole life.

I tried the 'paleo diet' - began 4 months ago. My normally regular & happy digestive system has been in revolt. I don't miss bread or pasta or cookies, but I crave chocolate still and wine. I've minimized my wine intake to one bottle/week. I'm almost to where I want to be - down to None.

My body's response?

I need some carbs. I do. Rice, sweet potato. My body loves & responds well to most vegetables & big salads. That seems to do it. I cannot tolerate much red meat but my body loves fish - particularly sushi. I am no scientist - I don't know why - but I know what makes me feel healthy and what makes my systems go haywire.

I feel full now after I eat, when - before - with more carbs of the gluten-based/sugar sweets type - I was hungry ...always. Or not hungry, really - but I had lots of appetite - which is different. Very different. And there is a huge connection even when I drink wine, now that I've isolated it, to intake of food and appetite. Not hunger again - but Appetite or craving.

My sugar sensitivity (to wine/alcohol) has increased with the decrease in drinking it. As I said, it's my last real link to what I would call 'bad' sugar.

What has become clear - however I'm wired, chemically, I guess one would put it - sugar is poison for me. And something in my system is out of whack in its relationship with sugar. I would call it an addiction to sugar, for sure. But what does that mean in terms of your talk of leptin & insulin? I couldn't explain - I'm sure you could :-) Certainly, hypoglycemia was an issue when I was eating lots of carbs - but no more since I stopped certain carbs & sugars.

And clearly, sugar spikes my appetite. And the more I stay away from it (which has been a struggle), the better I feel..but it's a weaning process. And the answer has not been no carbs at all.

I feel, somehow, this has to be related to stress, too. I won't go into why I feel that - I just feel it in the way my body works & responds to stress.

It is also all related to how much movement I get too - when I move - run, walk, do yoga, etc. - this decreases the stress, decreases the appetite for bad carbs (if you will)...but if I eat them, they still zing me & increase my 'appetite.'

Quite possible - but what kind, and in what quantity, and through which mechanism? For instance, is it fructose that´s the villain? Or carbohydrate and PUFA:s in combination? Or hyperpalatability induced by various carbohydrate-fat combos.

As stated by Stephan in the post, the issue is not the effectiveness of low-carb (it often works), it´s the chain of causation.

I'd like to share one more thing, because it seemed like such a contradictory experience of my relationship with carbs.

When I was going through my divorce, I couldn't eat. I was so stressed that all hunger and appetite shut down. I couldn't touch or think of anything food-related without feeling ill. The only thing my body would accept? Pasta or rice. And butter and salt. And water.

I couldn't think of cookies or ice cream or cappuccino or alcohol without a wall of blankness hitting me. Like a big "no." This lasted for 6 months. I lost so much weight, I was a perfect model size 0. Not anorexic, just what I would call very fashionably thin. Not healthy, though, despite what fashion might say.

Also, my skin had never looked so good. Go figure.

When I started feeling I could eat again, of course all of the weight came back (and a bit more)...as did all of the old 'cravings.'

I remain fascinated with why this could have worked. I suspect it has to do both with a logical process - i believe carbs release energy quicker and my system was starving and couldn't process anything complex (?). But I couldn't even think of any other food - not a vegetable, not a cookie. Which also have carbs...and sugar. Interesting.

I appreciated this. I this answered a lot of questions I have had in a clear and understandable manner. I would like to hear more about amylin because it seems like it is a key player in the obesity issue, and I haven't seen anyone write on it yet.

"Waitwaitwaitwaitwait. Everybody stop for a second. You can *fry* rice in butter? You mean to tell me that I've been boiling it all this time like a chump?"

=========================

True story...went to a sushi place - one of those place where they cook at your table-side while deftly juggling knives in the air to the delight of all.

Dude throws a bunch of cooked rice onto the hot grill along with an ENTIRE STICK OF BUTTER. Adds a little onion and mushrooms to the mix and fires it all up. Then proceeds to divide that between just two humans! Lots of rice and half a stick of butter in each portion!

How much butter would you eat if I handed you a stick of butter and said bon appetite baby! Probably not much.

But humans WILL eat that much butter when combined with nicely seasoned rice.

So perhaps carbs do drive overeating, in that they often drive you to over-consume fat, and hence too many calories.

@Bryce: Acetyl CoA is a central molecule in metabolism. It is the byproduct of both glycolysis and the "fatty acid spiral" (beta oxidation of fats) that feeds into the Krebs cycle.

De novo lipogenesis is also not the same thing as adipogenesis, if you will. And even that last term is often used to describe the differentiation of pre-adipocytes into mature ones and not the increase in adipose tissue. Obesity involves the increase in number and size of adipocytes and the degree of lipogenesis (fatty acid synthesis from AcCoA) has little bearing on this in humans.

obviously you could make triglycerides from the acetyl coa that resulted from metabolising the small amounts of glucose you would produce from gluconeogenesis on a ketogenic diet.

So the idea would go: on ketogenic, you can only make a finite mount of fat, limited by the small amount of acetyl Coa you had leftver from metabolising glucose in the brain. These acetyl's convert into the glycerol backbones that make up triglycerides.

THis is all, again, just what I've heard espoused by low-carbers. I don't know if you can ingest acetyl coa, or if you can use the glycerol bakcbones found in animal triglycerides to make your own trigs. If so, it seems you'd still need to ingest a colossal amount of fat to store fat? 1 molecule of glucuse would yield one acetyl coa, and so would a single triglyceride, but that triglyceride would be much larger and more calorically dense, and thus carbs would provide far more triglyceride backbones, isocalorically speaking, than dietary fat could.

To reiterate, I'm not espousing the above theory, I'm asking if anyone can discuss it, because I've heard it before (I think both taubes and eades have put it forward in different places?).

Stephan, awesome job. What is funny is that many people had been debunking this already (Colpo, Carbsane, Kreiger, Alan Aragon, Lyle McDonald...) but obviously, they all were incompetent individual, random blogger that no one should listen to. Since you have more respect from the community, i'm hoping the message shall be heard once and for all :)

Stephen, I don't have the time right now to do justice to this. However, you make one point that I have to refute.

Mild hypoglycemia is extremely common in people who have the genetic profile that goes on to become Type 2 diabetes. It can be detected in their 20s when they are slim. It isn't how low the blood sugar drops that creates hunger, it is the speed. Sugars dropping fast make the brain put out the message "Eat carbs, danger ahead."

I don't pretend to understand the underlying physiology. Taubes lost me with his hypothesis, though I have to also say that you aren't correct about the insulin response to protein. It is only relatively "high" in people with completely normal insulin resistance. In people who are highly insulin resistant the insulin response to carbs appears to be much higher than that to meat. That is why a low carb diet will eliminate the reactive hypoglycemia that drives hunger in people with insulin resistance.

The bottom line here is that there is a huge range in metabolic responses based on underlying physiology. What makes a person with an insulin resistance or diabetes gene fat may not be the same as what makes a person fat who doesn't have that underlying genetic profile.

Lumping everyone together, as is so common in discussions of optimal diet, is the real error here. And it is worth noting that the isolated populations you and others cite when studied for diabetes have been found to have completely different genes broken, so that the natural history of the "diabetes" they get is different from that of western populations.

The Pima, for example, develop retinopathy at a much higher blood sugar level than Western Europeans because their diabetes is caused by a unique set of disturbed genes found only in Pima. Ditto pacific islanders.

I say we need a richer vocabulary (or more complex model) than merely "good-tasting food".

Indeed, I´d say most of the stuff that I am prone to overeat is hardly a fantastic taste sensation compared to many foods that I have no overeating problems whatsoever with.================================

Can you please give an example of the bland foods you find too easy to overeat?

Stephan, in Part II you make a leap I don't think you explained. I was wondering if you (or someone) could clear it up.

At the end there, you seem to imply insulin spikes somehow indicate how much energy expenditure, energy intake or both there is in the body. As a hormone, insulin is a signal, an indirect influence on expenditure/intake, not a direct participant in the process itself. Is that incorrect?

To dumb it down for laypeople like me, the starter in my car (insulin) gets the engine (metabolism) running. After the starter turns off, though, the engine keeps going.

Frankly, I stopped reading after that because I rationalize the rest. Can you explain?

So does excess lipogenesis drive adipogenesis? Would this have bearing if the answer is yes?

As an aside, I've found that if I want to limit my carb intake at all, all I have to do is not season/butter/fry them. Steamed rice and boiled potatoes easily autoregulate their own consumptioon from a palatability standpoint. Score 1 for food reward ...

@ Kurt G Harris - Do you still stand by your assertion that, since diabetes is by definition excess glucose in blood...that transient spikes in blood-glucose levels following a high carb meal means you are "diabetic" for at least as long as it takes for your system to clear the excess glucose from blood?

And can glucose really do much harm when in blood for only short period of time? Don't proteins have to be exposed to glucose for at least a certain threshold of time for AGE's to form?

Bryce said - I've found that if I want to limit my carb intake at all, all I have to do is not season/butter/fry them. Steamed rice and boiled potatoes easily autoregulate their own consumptioon from a palatability standpoint. Score 1 for food reward ...

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Or score one for the simpler idea that better tasting food is MUCH easier to overeat than bland food. This stuff really is NOT that complicated folks!

Most of the bodybuilders I know, who I would consider to often be of much lower IQ's than the erudite commenters found on this blog, are MUCH leaner than most of you.

Why is that?

Because they aren't chasing their tail, running after all kinds of dietary theories about fat loss.

They simply RESTRICT CALORIE INTAKE. Some use an LC diet as an "automatic" way to do so. Some use a low fat diet to do it. Others simply count calories.

Really interesting- the article and the responses. Forgive me if I have missed this, but no one seems to be mentioning the gut-brain axis: I heard a study that talks about how obese people lean out when they have 'faecal' implantation from thin subjects, so what about the role of the gut bacteria in brain 'dysregulation'? What about the role of Candida overgrowth/gut dysbiosis in weight management? What about insulin surges in people with auto-immune and metabolic syndrome that is related to stress/cortisol? What about leaky gut and exogenous endorphins/opiates? I think the gut has just as big a role to play in why people become obese as the macronutrient ratio. Gut dysbiosis plus refined carbs plus damaged omega 6 have a big role to play in this whole debate. As someone else stated, no one gets fat on a ketogenic diet- and maybe this has to do with the normalisation of the gut flora?

To my simple mind Taubes theory makes sense that carbs elevate insulin which causes us to store fat, but in practice, why aren't all these low-carbers as skinny as a rail after eating this way for years?

Some stuff doesn't seem to add up (for the record I don't think carbs per se or post-prandial glucose or insulin spikes lead to obesity):

The satiety refs all use meals that are only slightly different and consist of foods that I (and probably you) don't even eat. For me there isn't a strong connection to macronutrients and satiety--eg, oatmeal, lentils, eggs, strained yogurt are all satiating--so with that I give little weight to those types of studies.

You mention brain-infused insulin, but how is that affected by macros? Lucas Tarfur of Ketogenic Nutrition recently did a good post about insulin and leptin signaling.

What is the overarching purpose with the insulin and REE argument? I understand that it helps disprove Taubes, but any general health inference here is tricky. Within the same refs, the same [high REE] is true with blood glucose and FFAs. Carbsane says the high insulin is there with a protective purpose, but I don't know...do we just slap the same reasoning on high blood glucose and FFAs?

There's a lot of evidence with lowered insulin and appetite and body fat. Lustig's experiments with octreotide are interesting. Petro showed weight isn't correlated with weight lost on a fast. A while back you posted a study that showed rats (or mice?) fed oxidized frying oils had mild hyperglycemia. But, those same rats had very low leptin, insulin, body fat, and liver trigs; they also ate less. I originally thought it was perhaps taste, but then they shouldn't be hyperglycemic? It's that oxidized fats inhibit insulin release.

The bottom line here is that there is a huge range in metabolic responses based on underlying physiology. What makes a person with an insulin resistance or diabetes gene fat may not be the same as what makes a person fat who doesn't have that underlying genetic profile.

Lumping everyone together, as is so common in discussions of optimal diet, is the real error here.

Thank you for that, Jenny. The commenters here who are blessed with genes that protect them from insulin resistance and diabetes may need to adopt a different dietary regimen from those of us who do have those genetic predispositions. Low-carb may not work for everyone, but it does work for some of us, and not just because of palatability issues. It relieves us of the relentless drive to eat every few hours, even though we may be so fat we can't waddle. I realize that for the metabolically healthy among us, relentless hunger is hard to understand, but as some of them pass into the realm of pre-diabetes, they will realize that this isn't just an academic discussion about the logic of shunning certain macronutrient food groups.

As a chronically underweight person who has tried to gain weight eating carbs, and lots of them, and failed--- I guess if it isn't really why fat people are fat it won't help skinny people gain weight either. :(

A good argument is well worth it, and this is a good argument. I'm frankly very glad Gary chose to challenge your ideas Stephan, and I'm glad for your vigorous response (and hope he makes one as well). Neither is completely convincing as I think you both have some holes to plug in the theory (and like many some tendency to avoid those holes), but are both contributing importantly to the answers (and seems likely there are more than one) as to why we get fat. Hope you both keep it up.

Thanks for your response Kurt...think you're right that I had you confused with "heart-scan" Dr.

Also think you're right that a bit of a glucose spike after a meal is not a bad thing. Though admittedly, he did kind of have me freaked out about transient rises in glucose after meals for awhile there.

I may have been commenting on the hazard of inducing muscle insulin resistance and then eating a large carbohydrate load. You can indeed achieve nearly diabetic levels of BG transiently that way and there are studies that show this happens. I and Peter at Hyperlipid have discussed this phenomenon.

I've searched on my site for it but cannnot find such. Context is everything.

The way Jeff has it paraphrased as a stand-alone I would not agree with it.

But it is true that if you switch from keto diet to high carb you will have higher pp BG for the first few meals during the transition.

don't meant to make this a question and answer session for you, but since you're paying attention over here, i would like your opinion. there's an argument coming from lc and vlc paleos that they are incapable of raising their carb levels- starchy carbs- because they automatically gain weight. i've started to hear this so much that i believe that some mechanism involving muscle insulin resistance that you spoke of recently is involved in this phenomenon. what say you?

my experience is being obese and because of that going vlc paleo for 3-4 months, then slowly introducing starches back in. now i have no problems eating starch on regular basis after a lifetime of them making me gain weight. could the fact that a person is vlc for years make them not tolerate glucose at all?

First of all: You state that low carb diets do indeed work well for weight loss most of the time, and that you see that as a fact. Kudos to you for acknowledging it. However, you can't say for sure why they work, if not through insulin, so maybe we should not rush to conclusions yet.

You also claim that obesity and metabolism researchers do not take the carbohydrate theory seriously. Well, as they have so far failed spectacularly to come up with anything useful for obesity I'm not sure that is a bad thing.

In the face of massively increasing obesity rates there is only one drug approved in Europe (where I work as a doctor treating obese patients), orlistat, and everyone pretty much agrees that it sucks. The only solution proposed is to cut away healthy stomachs to stop fat people from eating. Yikes.

The failure of obesity and metabolism researchers during the last decades is of epic proportions. It makes the Hindenburg look like a success story. Please don't tell me we should care what they think.

On to your three so called "falsifications":

1: Take a look at Robert Lustig's lecture during AHS. Hyperinsulinemia gives leptin resistance.

Problem solved. Moving on:

2. Insulin results in fat being pushed into fat cells BUT insulin also signals satiety in the brain... problem? No. Like most hormones (cortisol is a good example) insulin has short term and long term effects:

Short term it increases satiety in the brain. Makes perfect sense as it normally means that we just ate.

Long term hyperinsulinemia, on the other hand, increases fat storage and makes us eat more. At least partly through the resulting leptin resistance, like professor Lustig pointed out.

Again, problem solved. Nothing "falsified".

3. You claim that not just (especially refined) carbohydrates increase insulin, so does protein to some degree. Sure. But we all need protein and low carb diets are mainly about switching carbs to fat. Carbs release lots of insulin, fats do not.

There are plenty of studies showing that low carb diets drastically reduce insulin levels during the entire day. If you'd like references just say so.

Again, nothing falsified.

To summarize:Of course not all carbs are evil all the time. But refined carbs (sugar, easily digested starch) can be a huge problem for sensitive people (obese, diabetics). It seems we agree on that, as well as that low carb diets can be most helpful in those conditions.

What is really being questioned here is the explanation behind the way the world works. And perhaps it is not quite so simple as Taubes and others once thought.

However, if we complicate the theory just a little bit it still works fine. Let's not rush to "falsify" a working hypothesis when we have nothing better to replace it with.

If you go from VLC to say, 15% CHO I would expect you to gain some weight, in the sense that your setpoint might rise a bit just going to a not-ketogenic diet. If you keep gaining after that, then looking at the form and preparation of your starches would make sense.

Adding heavily buttered mashed potatoes vs plain white rice might well have different effects. If we think, as I do, that LC works for weight loss partially via food reward, we have to be careful not to alter the "food reward load" when we add back any carbs to the diet.

Lightly salted white rice is a good starch to start with. It's not the best nutritionally, but if you are eating mostly animal products and some greens it's usually well tolerated. YMMV

It's a hard question to answer without knowing all the variables. It also depends on if you are talking about body composition in the vanity sense vs actual obesity.

Stephan, I have a question about Part II of this post. You said that fat tissue is insulin resistant in the obese, but isn't Taubes hypothesis focused on muscle tissue becoming insulin sensitive before fat tissue does? Wouldn't that explain how someone becomes obese and then their fat tissue also becomes insulin resistant later when they are obese?

"could the fact that a person is vlc for years make them not tolerate glucose at all?"

I ate VLC for two years. As I blogged, mild orthostatic hypotension and limited tolerance for extended hours of hard labor ( not just working out) was the only side effect I ever had. I transitioned to 15-20% CHO and now 50% (as an experiment) with no significant weight gain.

I seriously doubt if you can permanently damage your ability to "tolerate" glucose by being VLC for years, unless you are or were actually diabetic to begin with.

You're clearly passionate about this issue and willing to put time into it. Why don't you use that passion to read the literature and create calm, well-referenced responses? No one is going to pay attention to you if you continue seasoning your posts with ad hominem attacks.

Take your passion and use it constructively to go the extra distance and fully research and reference all of your claims.

Stephan: One question: Assuming that GT’s carbohydrate hypothesis is complete nonsense, what are the implications for those of us non-technical souls who are just trying to find a healthy way to live? GCBC/WWGF has clear implications based on that hypothesis. My takeaway was that I quit wheat, rice, and most other starches (I never had much sugar and still eat plenty of meat, nust, veggies and certain fruits without counting calories). However, is entirely compatible with the image you blogged about earlier: “Don’t Eat Processed Crap – Juice and Soda are sugars”. This is also compatible with the messages in Mark Sisson or Kurt Harris’s blogs. In addition, this lifestyle helped me get off a TON of T2 diabetes medication with horrible side effects on me which I suffered through for 5 years. In addition, all the standard metrics (A1C, Lipids etc.) are perfect. Something that wasn’t the case for at least 5-6 years. That aint nothing and frankly, I am grateful for that. So what is your view of the implications of assuming carbohydrate hypothesis is utter nonsense? Does it mean a radical rethinking out the above approach? Or some modifications around the edges? Ultimately, the “correct” answer has to be translated into a framework for a healthy lifestyle which most of the population can put into practice. I would very much appreciate your thoughts on this.

BTW - I hope Stephan doesn't take my comments about "intellectual masturbation" the wrong way, as they were NOT being directed at him, his food-reward hypothesis.

I understand that Stephan writes for a very well read audience, and theses kinds of discussions are interesting and probably constructive among that crowd.

However, I think this kind of talk just confuses the hell out of the average Joe and Jane, who end up throwing up their hands in frustration, and saying to heck with it.

I am just a fairly simple-minded personal trainer with no advanced degrees, but find that I get my clients BETTER fat loss results by focusing them like a laser beam in their CALORIE INTAKE, rather than trying to get them to change the COMPOSITION of their diet right off the bat.

I spent years getting only so-so results by focusing too much on diet-composition, rather than calories. But since switching to a tight focus on calorie control, and having clients keep an online calorie journal that I check regularly, results have been MUCH better in terms of weight loss. Not to mention long-term compliance.

StephanThank you for a very lucid explanation, although I cannot follow it critically, it is educational. I have a peripheral point about thermodynamics which in no way counters anything you say here but if I am right invoking the first law of TD is not helpful. Conservation of energy is not really a universal “law”. Beyond HS physics conservation is understood as a very useful concept but not universal and there are analytical (math) tests for that. The law is true for the most part in inanimate systems and surprisingly widely applicable (hence belief that energy is a physical observable). The key point is that in engineering say, the practical importance of these laws is that if the total energy can be appropriately/accurately partitioned (by measuring & deduction) then it becomes possible to solve for the unknown parts of the equations. Is it possible to write detailed conservations laws for living organisms (in vivo)? I suspect not. Still energy will be conserved for the most part even if not understood in detail. But it is not practically useful (if my above reasoning is correct) for making fine distinctions as seems to be the ongoing debate and may contribute to unnecessary scepticism about biological explanations. From a personal prejudice viewpoint, experimentation is the most effective way to find what works or not and very few bloggers (Dr. Harris and P. Jaminet are shining exceptions) provide useful information on how to proceed. As education your blog is exemplary. The opinions of the amateur microbiologist posters is hilarious and often amusing.

It is very interesting to hear about your experiment eating 50% CHO, especially after you were VLC for so long. I'm not too surprised you didn't gain weight, but do you have any other comments on the experience? Maybe effects (positive or negative) on mood, energy, exercise, hunger, etc..? Or do you really think that for a healthy person it is functionally equivalent getting energy from either starch or LCSFA?

Do you think you'll continue eating 50% CHO indefinitely? Or will you probably add back in butter/cream eventually and settle somewhere between 15%-50% carbs?

If/when you resume blogging, I think many people will be interested in hearing about your experiment!

Thank you for acknowledging benefits of LC diets. Your series about rewording food caught my attention on a first place,because initially high carb diet didn't caused my weight problem, I never had a sweet tooth, but a salty one.However, in order to stop eating frequently and eventually to be able to eat only 2 times a day and practice IF, I had to do LC first for a while, it was the only thing to stop my uncontrollable appetite. Probably, naturally thin people like Kurt G. Harris MD just don't realize how powerful urges to eat could be for somebody on a chubby side from an early childhood. I am at complete control now first time in my life (I am talking about food and appetite) . Also, food is much less stimulating and rewording for me now,even salty kind. If benefits of LC are not explained by insulin theory - fine with me . My #1 experience says that even though carbs are not necessary the root of the problem on the first place, carb limitation can be the perfect cure easy to apply due to its ability to curb hunger.

On another hand, LC itself often is not enough. Many people experience a plateau after initial loss of 20 lb, as it was my experience for 2 years. Which was not so bad - in is better to have a constant reduced weight then a weight regain, as it happened with me before after low-calorie diets .It is the moment to start incorporating the IF and the theory about a food reword in order to get things moving again. I noticed, for example, that a meal of 2 soft-boiled eggs with 1 Tbs of butter is very satiating, while scramble eggs with tomatoes and garlic are not. Is it because of more intense taste or due to the carbo-content of sauteed tomatoes makes little difference to me.Unfortunately, winning the personal battle against obesity is never a simple process and using just one theory may be not enough.I hope my post is not too much out of topic.

Could you , please, tell, did you notice any difference between your fasting BS while on VLC and on higher carbohydrate diet. As far as I remember , Peter Hyperlipid said his fasting BS was lower if he ate some starchy veggies with his dinner.

It's very nice to read about all your theories, it reminds me of honey bees trying to figure out why they collect pollen.

It is the trees that provide us with the air we breathe and the food we eat. Perhaps it is also the trees, that, when they saw us eating the fruit, in their branches, that decided to grow a little higher up so that we had to stand on two feet to reach our food.

After all, Homo sapiens has not been on this Earth for more than 150,000 years, whereas nature has been here for billions. Do you ever wonder why it is that chicken liver tastes the same as beef liver and Cod liver? I would hazard a guess that Dinosaur liver also tasted like it as does shark liver. How do you explain the fact that the liver preceded Homo Sapiens by at least 500 million years?

Perhaps humanity is not in charge of itself, perhaps our job is to propagate the universe with our kind, because our benefactors, the trees want to spread their seed throughout the cosmos.

Thus you have a grand plan, not by humans, but by nature. The cream of humanity is driven from all corners of the Earth to North America and then UP into space. The moment this happens, or less than a year afterwards, the OPEC crises starts, and man is kept busy with trying to cope with everyday life.

Obesity, ADHD, Schizophrenia are not 'diseases' when one is on board a deep space vessel unable to go outside for a morning jog. However, it appears that rocket science, a technology that should have been abandoned decades ago has cluttered all your minds. Obesity is the way the South Pacific Islanders survived food shortages as they paddled in their outriggers in the vastness of the Pacific, much like a space craft. Mars has never been the objective of Nature, it is Faster than light travel that has been quashed by another Gaia. We should be using these 'abilities' to do the job nature intended us to do, to spread our seed and theirs throughout the cosmos.

thanks for your answer. i also experienced mild bouts of hypotension and inability to work out at the same clip that i did early on being vlc. i used that as a signal that my body was ready to start accepting starchy carbs again. in fact, i lost the majority of the weight i lost AFTER i started cycling starchy carbs. i think once the metabolism is fixed, you can start to implement them while still pushing down the setpoint.

I strongly disagree with your assertion that we shouldn't throw the carbohydrate/insulin hypothesis of obesity out the window because (1) we can't rigorously falsify it and (2) we have no alternative hypothesis. This simply isn't how science works- we need to admit that we currently have to testable hypothesis which fully explains the underlying biochemical mechanism(s) of obesity.

Nevertheless, low carbohydrate diets can be used to treat patients for obesity and diabetes, since it clearly does work. We can do this without saying that carbohydrates are the underlying cause of obesity and diabetes.

I greatly enjoyed your talk at AHS, and I think your success in treating patients with LCHF is remarkable, but it's important to not make the illogical leap from "low carb can treat obesity/diabetes" to "high carb diets cause obesity/diabetes through hyperinsulinemia."

"Therefore, if insulin doesn't increase energy intake (if anything, the combination of insulin and amylin that the pancreas releases in response to carbohydrate decreases it), and doesn't decrease energy expenditure (if anything, it increases it), then how exactly is it supposed to cause energy accumulation in the body as fat? There is no energy fairy. Obese people are obese despite having higher fasting insulin, not because of it."

This all appears to be off the back of short term work. While we know that a high insulin environment over time stimulates insulin resistance. Does the gradual down-regulation of insulin receptors not undermine this entire chain of thought ?

I'm quite certain Lustig got that backward in his talk (the idea that insulin suppresses leptin signaling in the brain). He had it right on one of his slides, but then somehow by the end it was reversed. It is common knowledge among obesity researchers that insulin and leptin act synergistically on hypothalamic neurons that regulate body fatness. See this paper for example:

http://www.ncbi.nlm.nih.gov/pubmed/12609497

The drug Lustig used to suppress insulin secretion, octreotide, is a somatostatin mimic, and has many effects besides suppressing insulin secretion. Also, if you look carefully at his slides, there was a subset of participants that gained weight on the drug. However, he only focused on the subgroup that lost weight.

I agree wholeheartedly with Dr. Lustig that sugar contributes to fat gain, but insulin is not the mechanism.

"do you really think that for a healthy person it is functionally equivalent getting energy from either starch or LCSFA?"

That is my current bias, yes. If you look at the distribution of fuel sources across evolutionary biomes as well as in the seasonal dimension, there is a roughly inverse correlation between availability of starchy plant organs and animal fats.

Stephan, you have opened a can of worms, which is the ultimate best outcome until everything is known, and I thank you.

I am just a ex-obese person who is always hungry.

Back to the science for two questions. Does internal starvation / glucose partitioning not all depend on the relative insulin resistance of fat vs muscle cells vs brain?

How much of this is implied insulin level from blood glucose verses actual measured insulin levels?

Some of the hunger seems to be related to what I think is the liver glycogen on board, depleted /repleted liver status. Any ideas on a N=1 test? A mono potato diet can only last for a few days, but the hunger is less on a mono potato diet with a bit of butter. Rice makes BG go wild.

And as far as food reward goes, I just don't get it. Eating the same amount of macronutrients should effect your fat storage the same way, unless, or course, the "bland" diet causes you to eat less. But what happens if you eat the same amount of macros "bland" and "tasty"?

Simply restricting calories has not helped me maintain a lower weight. I have gained, lost and maintained at 2300 calories and at 1100 calories, with no rhyme or reason.

If all the the food reward theory does is get me to eat less, I can do that all on my own without my food having to be bland. Sometimes I lose on lower calories, sometimes I gain.

And if all the carbohydrate theory does is get me to eat less CARBS, I have done that and it sometimes results in weight loss and sometimes results in maintainance or even gain.

But in both cases, eating a small amount of food is not sustainable (I starve all day) and eating high carbs makes me ravenously hungry an hour after saying, "I'm so full that I'm never eating again!"

My last little bit - To say that weight gain is always caused by overeating is just plain silly. There is obviously something else going on when a person has to eat like a bird to even maintain weight. When you sit down with a group of people, eat the same meal as they do, and find that you are 3 pounds heavier the next day and that everyone else has maintained or even lost weight, it is obvious, at least to me, that there is more to weight gain that eating too much and not moving around enough.

Maybe it is driven by hormones, and not by the amount of food that is eaten, as Gary says.

Stephan,"I'm quite certain Lustig got that backward in his talk (the idea that insulin suppresses leptin signaling in the brain)... It is common knowledge among obesity researchers that insulin and leptin act synergistically on hypothalamic neurons that regulate body fatness."

I talked to Lustig about this and yes, sure, like I wrote above, the short term effect of insulin is appetite suppression – and it makes perfect sense as high insulin is normally a signal that you just ate.

However, Lustig is saying (both in his new talk and when we spoke) that a long term effect of hyperinsulinemia is leptin resistance. He claimed that many researchers are starting to accept this.

Of course this would mean that the leptin- and the insulin-theories can both be true.

"The drug Lustig used to suppress insulin secretion, octreotide, is a somatostatin mimic, and has many effects besides suppressing insulin secretion."

Ok. Then how about the fact that diabetics injecting pure insulin, nothing else, tend to gain weight? A very well known side effect... And how about the fact that type 1 diabetics, lacking insulin, lose weight rapidly?

Please continue your intelligent and careful study of the obesity problem. It's great to read a well thought out response that keeps me thinking.FYI-I've added back potatoes & rice to my diet and the weight is still coming off. I have not, however, added the wheat, sugar, dairy or oils back though.

"it's important to not make the illogical leap from "low carb can treat obesity/diabetes" to "high carb diets cause obesity/diabetes through hyperinsulinemia.""

I still think that is the best possible explanation we have so far.

BUT of course a lot of people (like Asians, Kitavans, you name it) have been eating a high percentage of unrefined carbs with no problem. So it obviously takes more than just rice or tubers to start the problem. Combining sugar, refined starch and lower levels of physical activity seem to do the trick though...

Hyperinsulinemia does not cause leptin resistance to my knowledge, however, hyperinsulinemia is a symptom of insulin resistance, which could hypothetically contribute to leptin resistance. This is a persistent problem with the carbohydrate hypothesis, it does not properly account for the role of insulin resistance in intracellular insulin signaling.

The point is that reduced insulin signaling due to hypothalamic insulin resistance could contribute to letpin resistance, consistent with the overlapping roles of insulin and leptin in the hypothalamus. That is a totally plausible hypothesis.

But then we're left with the question: what causes insulin resistance? That factor is not carbohydrate per se, although refined carbohydrate and sugar may contribute.

Both low-carbohydrate diets and diets high in unrefined carbohydrate and fiber have the ability to reduce body fatness and improve insulin sensitivity in insulin-resistant people.

Acute and chronic effects of insulin on leptin production in humans: Studies in vivo and in vitro.

This study was undertaken to investigate the changes in obesity (OB) gene expression and production of leptin in response to insulin in vitro and in vivo under euglycemic and hyperglycemic conditions in humans. Three protocols were used: 1) euglycemic clamp with insulin infusion rates at 40, 120, 300, and 1,200 mU / m / min carried out for up to 5 h performed in 16 normal lean individuals, 30 obese individuals, and 31 patients with NIDDM; 2) 64-to 72-h hyperglycemic (glucose 12.6 mmol/l) clamp performed on 5 lean individuals; 3) long-term (96-h) primary culture of isolated abdominal adipocytes in the presence and absence of 100 nmol/l insulin. Short-term hyperinsulinemia in the range of 80 to > 10,000 microU/ml had no effect on circulating levels of leptin. During the prolonged hyperglycemic clamp, a rise in leptin was observed during the last 24 h of the study (P < 0.001). In the presence of insulin in vitro, OB gene expression increased at 72 h (P < 0.01), followed by an increase in leptin released to the medium (P < 0.001). In summary, insulin does not stimulate leptin production acutely; however, a long-term effect of insulin on leptin production could be demonstrated both in vivo and in vitro. These data suggest that insulin regulates OB gene expression and leptin production indirectly, probably through its trophic effect on adipocytes.

I think the point is that the reasons for obesity are just not well-understood, and that we're talking about a rather complex system, here. In short, we may well find out (eventually) that there is no one-size-fits-all solution and that different people have different phsiological characteristics that have to be taken into account.

Debunking a theory is one thing, but does it help to advance us towards the right theory?

Excellent post Stephan! It seems like Taubes' lasting contribution will be to have debunked Keyes' lipid hypothesis. As far as low carb diets helping people lose weight it seems like these diets are hypocaloric because the fat leads to a feeling of satiety before you can overconsume calories. It just seems like there have been thousands of people who have benefitted from the Atkins approach to combating obesity.

With that being said excellent work debunking the "carbohydrate hypothesis"!

The whole "traditional"/"paleo" nutrition community is a bit wack now. The "nice" answer to everything seems to be "everyone is different," but others need to hear the same answer from all of their gurus. Stephan has been pretty much at the forefront of the "macros don't matter" crowd and has presented a new idea over the past few months. Now he's been put into a position where he feels it necessary to debunk the insulin/carb hypothesis although everything in this post he has already said.

While carbs obviously play a role, many things stimulate insulin production: short chain fats, salicylates, certain aminos, etc...same with blood sugar, insulin-like activity, etc. This gives any type of "carbohydrate" hypothesis rough edges, especially since insulin does not exist solely to react to dietary carbohydrate. However, as tiago mentioned, as well as I earlier, there are some things, like the diazoxide study, that seem to be quite clear and in favor of the [fasting] insulin hypothesis, despite cryptic observations of brain-infusion-induced satiety or higher FFAs in obese. I know for myself that certain foods are more satiating per calorie or gram; it's not dependent exclusively on macros; I don't know if it's dependent on glycemia or insulinemia, as I don't measure. I understand why Stephan felt the need to write this response, but I feel like we're taking a big step backward. It's funny how when Petro, Stephan, Kurt, Don, etc all agreed, eveything was fine and dandy, but now that Don and Stephan have changed views, everybody reverts back to arguing about macros and looking at stupid studies where one group eats toast, margarine, and orange juice while the other group eats toast, chocolate skim milk, and home fries. If you don't think your high fat diet "works," don't do it; if you don't think your high carb diet "works," don't do it; nobody else knows all the foods your eating and all your other behaviors. If I agree with Petro about the cause of obesity, great, but that doesn't mean I want Stephan to stop writing anything contrary or that I feel his writing is a personal insult. Can we please get back to developing new ideas and analyzing new information, instead of talking about how the carb hypothesis is "right" because "I ate [whatever] and gained weight"?

Stephan,"Both low-carbohydrate diets and diets high in unrefined carbohydrate and fiber have the ability to reduce body fatness and improve insulin sensitivity in insulin-resistant people."

Sure. And what is one of the similarities between those diets? They are both low in pure sugar and other refined carbohydrates, especially compared to modern western diets. So I fail to see how that is falsifying anything.

I am not Mat Stone, if that is what you were suggesting. I don't even follow his obnoxious blog.

I have another issue with this delineation of the problem: It's too focussed on the one or two things insulin does that you know about.

Insulin does all sorts of things, different things in different cells. See here: http://www.ncbi.nlm.nih.go​v/pubmed/10583426

You are taking issue with Taubes laying ALL the bad effects of carbs on insulin. I agree that's probably wrong. There are lots of hormones doing all sorts of things that may play a role (eg Leptin, as you suggest).

But to deny that insulin plays a role, while ignoring how it up and down regulates over time and while ignoring all the other things it does in various tissues to me feels just as wrong as laying all the blame at its feet.

Stephan,"But then we're left with the question: what causes insulin resistance? That factor is not carbohydrate per se, although refined carbohydrate and sugar may contribute."

Ah, the million dollar question!

My guess: too much refined carbs and sugar for a long time, combined with insufficient exercise (which would have burned the carbs), combined with a genetic vulnerability.

Speculation: The chronically elevated insulin combined with already filled-up glycogen deposits makes the cells down-regulate the insulin receptors, as only a few are needed under those circumstances.

Thus: The elevation in the insulin levels and the insulin resistance would develop hand in hand. And then we can argue about what is the chicken and what is the egg, while in reality (if this is true) they happen at the same time.

I have followed this debate for what feels like years. I've watched the finger point in nearly every direction: first it was calories, then it was carbs, then it was fat, then it was carbs again, now it's processed food. Maybe we're reaching the point of capitulation. Maybe we can't develop an overall position because the problem is too complex and individualistic and driven by too many factors - genetics, endocrinology and on and on. The various camps in this debate keep slinging it out - and there doesn't seem to be a definitive answer.

And Andreas, maybe I have misunderstood something essential since I understood that Gary Taubes has made three g e n e r a l assertions given in the beginning of the Stephan's text.

As you (should) well know, a stament can be falsified by finding a counterexample to that one, and this is what Stephan does (and much more). You, Andreas, just gave some special cases where Gary's statements are true, thus your argument does not falsify the falsification by Stephan.

This is a terrific post and really informative comments. I really appreciate the contributions from InWoo2 as well, despite the clear exasperation in their tone. I agree with an earlier comment, that this sort of detailed discussion of the state of knowledge of obesity physiology is hard to come by. What makes GTs contribution so valuable is that he did the hard work of sythesising a lot of science for the lay person. Scientists rarely do this because (1) it is hard and (2) it won't advance your science career. Nonetheless, GTs carb/insulin hypothesis is too simplistic, and this post does a nice job of dissecting it.

As informative as I find your discussion of insulin, I am not persuaded by your dismissiveness of the role that insulin plays in obesity. Insulin is a complicated beast, and leptin is only one of many additional hormonal players that is driving fat metabolism dynamics. The food reward theory is very interesting, but I just don't see how it explains the fact that some people are more susceptible to obesity than others within the same obesogenic environment. There is much more to the physiology that needs explaining, in my opinion.

Thanks again for all the work you put into this blog. It is much appreciated.

From what I can find in the litterature, it seems like IR is secondary to lipo and glucotoxicity and the death of beta cell, to make it very short (and clearly all the mechanisms are not very well understood as of now).

I have not, to my knowledge, ever saw a paper which claim that chronically high insulin level cause insulin resistance.

So this is all speculation from Taubes et al. part, would you admit that?

On your first falsification of Stephan fasification, you say that he admit that LC diet work, but not trought insulin, but since he don't know why, the hypothesis could still hold. Well, what about the very well known fact that LC spontaneously reduce hunger and caloric intake?

The fact that obesity researchers can't come up with a single solution, as you seem to be after, probably mean that obesity is very complexe, has no single answer, and will never have. Why do you hold so hard to the idea that there should be a simple and single explation to a very complexe phenomenom?

Obesity has a demographic, enviromental, genetic, social, emotionnal, metabolic and yet others components to it. How do you think we can come up with something as simple as refined carbs to explain it?

As Stephan keep saying, most researchers don't take this hypothesis serisously because there is so much data arguing agaisnt it that you really have to be brainwashed to keep thinking it is right in the face of so much contradictory evidences.

The inhability of the human being to consider himself wrong and admit that he failed will never cease to amaze me.

I understand that it can look like an interesting hypothesis, but there are just too much data arguing againsnt it. So why not stop losing our time and seek somewhere else?

well,"As you (should) well know, a stament can be falsified by finding a counterexample to that one."

Naive falsification á la Popper... sure, if we are talking about the existence of black swans. But in more complicated scientific questions it is rarely quite that simple. In that case anything could fairly easily be falsified and we would know nothing. We have to make sure there is no problem with the counterexample first.

Frank,"Well, what about the very well known fact that LC spontaneously reduce hunger and caloric intake? "

Absolutely true I think. But why? That may be through reduced hyperinsulinemia and a resulting decrease in leptin resistance, making the brain "see" the big fat stores. (according to Lustig)

"Obesity has a demographic, enviromental, genetic, social, emotionnal, metabolic and yet others components to it. How do you think we can come up with something as simple as refined carbs to explain it? "

Lung cancer has all of those components. Yet something as simple as smoking is the cause in 90% of all cases.

While Stephan has convinced me that food reward is often a factor in obesity, I don't see that understanding it can be very useful to most individuals. Willpower doesn't work for most individuals when it comes to "eat less, exercise more", and so I don't believe that those individuals' willpower will be adequate to stop them eating their favorite foods. This is especially true when they are not in complete control of their home and work environment. Of course, I'm open to being convinced otherwise. Thanks, as always, for the great work, Stephan.

Well, Gary Taubes gave very simple general answers to a complicated questions, and therefore they are so easy to falsify. If he had restricted his assertions to some special cases, e.g. to those having hyperinsulinemia, maybe his assertions would be harder to falsify (as you showed) ;)

"Although it doesn't work for everyone, there is no doubt that carbohydrate restriction causes fat loss in many, perhaps even most obese people. For a subset of people, the results can be very impressive."

"However, once overweight or obesity is established, carbohydrate restriction can aid fat loss in some people."

Your statements above represent the main message I took away from my reading of Taubes' latest book, Why We Get Fat, and then acted upon to lose weight (40 pounds in 5 months so far). I realize that you are arguing about precise mechanisms, insulin's role, etc. You may be right in your analysis. Like Taubes, I'm not a scientist, so it's hard for me to judge. I'd have to spend weeks examining your sources and his, to no real point because I'm not even a science writer, but just a guy who cut carbs and lost weight and feels good about it. For an obese person, the bottom line in this discussion is about how to lose weight. For me, that bottom line is represented by this statement in Why We Get Fat: ". . . people who restrict carbohydrates often eat less than they otherwise might" (p. 211). And here you say almost the same thing: "Carbohydrate restriction spontaneously reduces calorie intake." That is precisely what has happened in my case, and it is the reason that I think a low-carb diet works for me. You acknowledge that a low-carbohydrate diet may suppress appetite, but say that it is not because of the insulin mechanism identified by Taubes. Fine. Explore alternative mechanisms. Extend human knowledge. It is a worthy enterprise. For now,for me, and for many over-weight people, the take-away message is the same as before: cut carbs to lose weight, and if that works, keep on doing it.

The current reason in the litterature as to why LC works so well is because by default these diet are higher in protein (and no, in real life most people just don't replace their carbs with fat, they clearly get more proteins) and that protein have a high thermo value, and a very positive effect on satiety and muscle mass. You also usualy get a lot of veggies which have a great density while being very low in energy, further reducing hunger. I don't see why it needs to be much more complicated than this as to why LC works very well. It's a much more plausible reason with much more data to back it up than the insulin hypothesis, if you objectively consider the available data.

Excellent post. One thing I'm wondering is if in a healthy person who consumes carbohydrates or protein immediately before low-intensity exercise, does insulin, acting through HSL, prevent lipolysis and force the muscle mitochondria to use glycogen as an energy substrate, even though the intensity of the exercise would normally be such that lipolysis could fuel it completely?

So, this is good information if you're concerned about solving or preventing an obesity problem, but how does it relate to inflammation and cholesterol? My impression from reading over the years is that arterial inflammation is one of the reasons the body produces cholesterol, and that one of the things that causes arterial inflammation is blood sugar.

Stephan, do you have a picture of how diet relates to inflammation, cholesterol, and heart disease? My father just had quadruple bypass surgery at 69 despite being thinner than I am, and I'm wondering what in his diet may have contributed to that. (Of course, he's fighting against his genes, but I hold out some hope that there is a significant dietary component here.) Thanks.

The mechanisms of how low carb diets suppress appetite is well established in the scientific literature. It comes down to 3 things:

1. Low carb diets are typically high in protein, and it has been proven in a very large number of studies that high protein intakes suppress appetite

2. There is an additional appetite suppressant effect from reducing carbohydrate to a ketogenic level, although this effect is much smaller than the effect from protein, and is highly variable from one person to the next. This effect likely does not last a long period of time since it is difficult to stay in dietary ketosis for extended periods.

3. The limited food choices and monotony can actually contribute to lower calorie intake. I will be writing an article on habituation, monotony, and its effects on calorie intake on my site soon.

This is not very convincing, although I do applaud the work you put into it to present the counter-arguments to Gary Taubes). This is called true science.

It seems a bit one-sided, that is the argument against carbohydrate hypothesis do not appear to be as solidly supported as those in favor. I am reluctant to spend too much time on it, just would like to point out 2 small examples.

If insulin is causing increased fat accumulation due to a decrease in energy expenditure (presumably because elevated insulin is locking fat away inside fat cells), then people with higher fasting insulin should have lower energy expenditure. Lucky for us, that hypothesis has been tested. At least two studies have shown that higher fasting insulin is associated with a higher resting energy expenditure, independent of body fatness, not a lower expenditure (14, 15). This is consistent with the idea that elevated fasting insulin opposes body fat accumulation, not that it contributes to it.

Those papers demonstrate higher resting energy expenditure (REE) correlating with fasting insulin, but not the reason behind it. That reason (higher night time glucose level) does not necessarily support your conclusion of insulin being supposedly the cause of it. The most likely cause is the high glucose (the diabetic "dawn phenomenon") triggering body to increase the REE to burn it off.

Furthermore, it is too farfetched and probably incorrect to draw second-removed correlations from this effect to weight gain or weight loss phenomenon.

There is a multitude of studies showing that hyperinsulinemia is a big health hazard for arteriosclerosis, hypertention, stroke. It is a health hazard by itself regardless whether it is accompanied by obesity (though in most cases it is) or without obesity (for example in my case).

Second example, from your article:

West Nile district, Uganda, 1940s. The diet consisted of millet, cassava, corn, lentils, peanuts, bananas and vegetables (Trowell and Burkitt. Western Diseases. 1981). Despite food abundance, "in the 1940s it was quite unusual to see a stout man or woman."

This does not seem to be adding for or against the hypothesis since there are thousands other factors involved. (I used to eat high carb plus high sugar and didn't get fat either). Besides, do the papers you quoted really show data suggesting that the Ugandans average nutrition in the 1940-ties was high caloric?!

Regardless of the outcome of this debate, I think it's safe to say that low carb is the best approach for a majority of the people looking to fight obesity or even to maintain a certain bodyfat percentage.I'm an Asian and lived the first 26 years of my life eating a typically high carb diet and was at a bodyfat of about 19% when I started low-carbing about a year ago. I'd been into weight training since my late teens so I considered myself pretty fit, even if I didn't have that 'ripped' look. After about a year of eating moderately low carb (close to 100g per day), I'm now at a bodyfat of around 8%. There were of course periods of conscious caloric restriction which is something you have to do to get REALLY lean; I don't know how people tend to think that you can continue losing weight endlessly without ever decreasing intake. The point is, I was never able to get the same results on a calorie restricted high carb diet, no matter how strict I was.The best part is that low-carb is now helping me maintain my low bodyfat despite eating like a horse. I love my fat and protein and consume well in excess of 3400 calories/day at a bodyweight of 160 lbs. It seems that no matter how much I eat, it's virtually impossible to gain bodyfat on this diet. In contrast, every calorie I consumed over maintenance level tended to show on me when I ate high carb. I don't know what's at work here, but I'll sure as hell take it!

Frank said, "Well, what about the very well known fact that LC spontaneously reduce hunger and caloric intake?"

That is only true if a person is coming to low carb from the Standard American Diet. People who come from a lifetime of dieting (Weight Watchers and other low calorie ways of eating) will experience a reduction for hunger FOR CARBS, but not a reduction of hunger for real, whole, unprocessed foods.

I frequent the Atkins Community Forum, and it seems like half of the women coming there have to be told that they will lose weight better if they stop eating like birds, myself included, when I first went low carb.

If a person is used to eating very little high carb, low fat food, that person will start eating MORE calories, not less, when they switch to low carb, high fat food.

Carnivore and Rebecca Latham are probably misjudging intake. Many, perhaps most, people overestimate intake if they switch to eating a lot of high protein, fatty meats and foods. While pretty calorically dense, a pound of meat is still usually only about 40 calories per ounce, even if it's something like bacon.

Carnivore said, "I love my fat and protein and consume well in excess of 3400 calories/day at a bodyweight of 160 lbs. It seems that no matter how much I eat, it's virtually impossible to gain bodyfat on this diet. In contrast, every calorie I consumed over maintenance level tended to show on me when I ate high carb. I don't know what's at work here, but I'll sure as hell take it!"

So it is possible to EAT MORE calories and LOSE MORE weight when eating high fat and low carb, than eating in the opposite way.

I think that Carnivore and myself are the only ones who believe that to be true, that have posted on this thread.

I have weighed, measured and recorded every morsel of food that has gone into my mouth for over two years since starting low carb, and every time I was on a diet before that I did the same thing. I am not misjudging my food intake. I even starting weighing my food using grams instead of ounces, because it was more accurate.

I was waiting to see if someone would say that it was not possible. I am living proof that you can increase calories and lose weight. I mentioned in another comment here that if I eat high carb and low fat, 1100 calories will maintain my weight, and if I eat low carb and high fat, 1800 calories will maintain the same weight.

This is a fact. n=1

So what you are saying is that if I was eating 1100 calories doing Weight Watchers (which I was), in order to lose weight eating low carb or any other kind of carb, I would have to drop down to, say, 600 calories in order to lose weight?

Just accept that for some people there is a scientifically measurable metabolic advantage to eating low carb and high fat. I eat more, not less.

CICO, in all it's beauty and simplicity (simplisticness?) does not apply to me and I'm not the only one.

no, i mean the caloric listings on stuff like the various calorie listing sites are not accurate, particularly for meats, though not exclusively. a lot of meat, for example, is assessed at 50-70 cals/oz when it's just not. so you go from starch heavy to less starch and think you've increased intake, but the metric is wrong.

Oh also, if you increased physical activity and NEAT concurrent with switching eating styles, you have a pretty huge confound as well. A lot of people completely change their activity levels with their diet changes and assume the diet is the sole driver.

It is interesting you mentioned monotony of LC food. On one hand, the absence of starches and sugar doesn't limit much an opportunity to spice up any dish and additional butter makes almost anything taste better, on another hand LC somehow chills down an excessive interest in food and desire to make it as tasty as possible. Nice change for me after long life of food obsession. Still, I like to cook, so my family doesn't suffer that much.

I don't eat food that has labels. I take my nutrient info from the USDA site.

And as I said, CICO in all it's simplisticness (and yes, that is my little derogatory term) does not explain the fact that I started losing weight by changing the macros and increasing the calories in my diet.

And I'm not the only one.

I don't disagree with the Laws of Thermodynamics. I am not saying that the TRUE MEANING of CICO is false. I am saying that the common understanding of the term is faulty, if the common understanding is that it is impossible to lose weight by eating more calories. CO changes based on CI. There is a metabolic advantage.

I evidently get more bang for my buck CO-wise, when I eat low carb and high fat.

And, obviously, I benefit by getting to eat more calories, because eating high carb, low fat and low calorie is like living in hell, where the main torture is starvation, all day and all night.

Let me sum up: I am eating more calories to maintain the same weight and I am not freezing cold and starving. Works for me.

"Oh also, if you increased physical activity and NEAT concurrent with switching eating styles, you have a pretty huge confound as well. A lot of people completely change their activity levels with their diet changes and assume the diet is the sole driver."

For the record, I did not change my exercise. I was not exercising at all at the time, so it's a no-brainer that my activity level was not a confounding factor.

It is disappointing to see Stephan post an article like this. The thinking is as slipshod as anything in the nutrition journals.

The big problem Stephan has is over-generalization. If a study has shown a link between A and B, Stephan assumes its an iron law that always holds. By analogy, suppose you are the doc in an ER and someone comes in gripped in the throes of an asthmatic attack. "She's not getting enough oxygen!" someone shouts. You, schooled in the Stephan school of science, calmly reply "That can't possibly be the case. I can cite 5 studies that show the human lung capacity is more than sufficient to provide all the oxygen you need."

And that's the trouble here. Not everyone loses weight on a low carb diet. But for those that do, might they be as different from the regular population studied in the journals dear to Stephan's heart as the lungs of the asthmatic are from you and me?

A little Johnny come lately on this, and more on the topic of palatability, but thought I'd share it here. Have you come across the hypothesis that agriculture spread because of 'the drug-like properties' of cereals and milk? Suggested by a pair of anthropologists and re-printed here: ranprieur.com/readings/ origins.html

This doesn't necessarily explain the obesity epidemic, since some populations have been eating cereals and milk for a long time without obesity. But it does touch on the reward factor of certain foods, which may interact with other factors and contribute to susceptibility.

It also may explain offer another point of overlap between the food reward theory of obesity and why certain iterations of low carb diets or paleo diets may generate fat loss, if they also reduce the presence of physiologically rewarding compounds in the diet.

May not be relevant, but I would love to hear your take if you have any thoughts to share.

If carbohydrate is the root of all evil, then babies are doomed to be obese and have metabolic syndrome because mother's milk contains carbs. It's like saying cholesterol is bad for the heart and mother's milk contains cholesterol, so the baby is also doom to have a heart disease when she gets older? I'm not a scientist, just a mother who is trying to make sense from the carbs hypothesis argument so that she knows what to feed herself and her family. I think the best model macronutrients to follow for a healthy human diet is human breast milk. So, no I don't buy that carbs are bad. Toxic modern industrialized food is what causes modern diseases. Just my 2cents.

So lets take refined white flour, unarguably bad for blasting BS through the roof (Taubes carbs/insulin), and feed it to a bunch of people for while in it's plain white state (Stephan's food reward) and see if people get fat?

My money is on Stephan ;)

After we win, I will invite Stephan over to make paper mache animals with all the left over flour and money we won. We'll then give the animals to the low-carb losers to help cheer them up.

You might control very well for your caloric intake, but you have absolutly no way of knowing your daily energy expenditure, unless you're telling me you've spent some time in a metabolic chamber figuring out.

This is something very important that LCarber fail to adress when they keep saying that they eat more on LC than they expend. How can you know? You can't. You don't know what your daily energy expenditure is. It vary greatly from individual, and diet can have an impact on it.

There are multiple studies totalising multiple subject readily available on pubmed showing that when substituing carbs for fat while keeping protein and calories constant, there is not effect on the rate/amount of fat loss.

There is good reasons why n=1 can't be use as evidence.

But all the LCarber can keep doing all the wishful thinking that they want, all power to them. I'm glad that LC helped yout out. Just don't make the mistake to assume that this is what everyone need, nor that it's the optimal way to achieve results.

My main issue with this debate is that LC works so brilliantly, a virtual magic bullet, for the conditions associated with insulin resistance. Not just overweight, but lipids, BP, PCOS, GERD, etc etc along with a host of inflammatory conditions, too. There is more to this than insulin, LPL and adipocytes. Way more.

In my own personal experience, after almost 9 years of VLC, I eat like a horse, I thoroughly enjoy my food, I eat heaps of fat including SFA, but nothing sticks unless I overindulge in carbs. Even nuts can cause me to gain adipose. I do have insulin resistance but since this is endemic in north america now, I am probably in the majority. It would appear that LC is the simple solution to a myriad of medical problems that are draining the collective coffers of society.

I realize n=1 doesn't get a lot of respect, but I have seen the same results in so many others that I have few doubts as to the validity of my observations. I also find lots of supportive literature, especially the carefully executed studies by Jeff Volek et al. In my own research, I have seen remarkable results, unlike anything achieved through other diets or pharmacology.

On balance, I find the explanations put forward by Taubes and Lustig to explain these phenomena more compelling than anything else I have encountered, including the notion of palatability and reward.

Dr J says: "My main issue with this debate is that LC works so brilliantly, a virtual magic bullet, for the conditions associated with insulin resistance. Not just overweight, but lipids, BP, PCOS, GERD, etc etc along with a host of inflammatory conditions, too. There is more to this than insulin, LPL and adipocytes. Way more."

This is of course very true. Like Andreas says, we should not throw out the baby with the bathwater. However, the same improvements Dr J mentions are seen when people with metabolic syndrome and all the related (downstream?) pathology are put on an ad libitum 'paleo' diet, regardless of macronutrient composition.

Bu there is one important difference. When people exclude Kurt's Neolitic Agents of Disease (wheat, sugar, concentrated PUFA's and I would personally add dairy to the list) patients experience improved insulin sensitivity and improved glucose tolerance. On a strict LCHF diet, insulin sensitivity and glucose tolerance decline, suggesting impaired insulin signaling. Andreas has proven this in his excellent n=1 OGTT (with the glucose coming from a lunch served at an obesity conference ;-) containing the usual processed crab).

My question has been for years: is this fairly well established low carb induced 'physiological' insulin resistance a bad thing, or just a benign adaptation to very low carb? I am inclined to see it as a normal, but not optimal adaptation. An important hallmark of healthy (long lived) populations is excellent insulin sensitivity and glucose tolerance. I therefore think it would be wiser to follow Staffan Lindberg's model than let's say classical Atkins. I'm very interested in Andreas' thoughts on this.

@Laura LeeAs a chronically underweight person who has tried to gain weight eating carbs, and lots of them, and failed--- I guess if it isn't really why fat people are fat it won't help skinny people gain weight either. :(

You might try a low-carb diet, seriously. Prof. Lutz (Life without Bread), one of the pioneers of low-carb had excellent results with underweight people by putting them on low-carb diets.

This shows imho excess carbs messes up metabolism, on some it will move setpoint in one way (ecxcess weight) on others in the other way.

this might not be completely pertinent to the carbohydrate issue, but i'd like to ask a quick question about food reward. In my case I've experienced the problem where due to the bland food i was ingesting I really did not want to eat anything. This caused a couple of uncomfortable problems, specifically, all those associated with undereating...no energy,etc. The only way, it seemed, was to eat highly rewarding food, or just not eat at all. Now i'm wondering if this is normal and just necessitates some kind of buffering period, or is there something else at play.

From my own personal experience carbs do count, calories do count AND food reward does count. Overweight really is a multi-factorial problem. I have big blood sugar problems and feel as if I'm having a heart attack unless I keep carbs fairly low. They also make me ravenously hungry. I also get IBS-type problems with too many carbs, even good veggies. BUT low carb doesn't keep me slim, I also have to count every calorie to lose weight. (Most people don't, but I am at an age when weight doesn't come off easily.) This is difficult as I love food and am a compulsive emotional eater... so the food reward idea will help me a lot. Foods these days are purposely created to incite craving - (I am currrently reading David Kessler's book which is v interesting). So thanks for your ideas Stephan, they will help a lot of people even if food reward isn't the whole solution for everyone.Carbs may not have caused my blood sugar problems, but eating them these days is a really bad idea. Just as running marathons might not cause a broken leg, once you've got a broken leg running marathons is a really bad idea. (Bad analogy but you get the idea!)My theory is that I have several types of 'hunger', only one of which is valid. My other hungers are blood sugar hunger, addictive hunger, psychological hunger... maybe others. (Then there's eating for social/political reasons. A whole other can of worms!!) Lowering carbs reduces the blood sugar hunger. Addressing the food reward issue may help with the addictive hunger... it really is horribly complex but getting ideas from many people will hopefully help in sorting my situation.

About Me

I'm a writer and science consultant with a background in neuroscience and obesity research. I have a BS in biochemistry and a PhD in neurobiology. I'm the author of "The Hungry Brain: Outsmarting the Instincts That Make Us Overeat".

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